Phenotypes associated with this allele

• Allele Symbol: Dmd^mdx
• Allele Name: X linked muscular dystrophy
• Allele ID: MGI:1856328
• Summary: 50 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dmd^mdx/Dmd^mdx	C57BL/10ScSn-Dmd^mdx	MGI:4359195
hm2	Dmd^mdx/Dmd^mdx	C57BL/10ScSn-Dmd^mdx/J	MGI:3621491
hm3	Dmd^mdx/Dmd^mdx	D2.B10-Dmd^mdx	MGI:5688354
hm4	Dmd^mdx/Dmd^mdx	D2.B10-Dmd^mdx/J	MGI:5697652
hm5	Dmd^mdx/Dmd^mdx	involves: BALB/c * C57BL/10ScSn * C57BL/Ka	MGI:5490615
hm6	Dmd^mdx/Dmd^mdx	involves: C57BL/10ScSn	MGI:2654139
ht7	Dmd^mdx/Dmd^+	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366785
ht8	Dmd^mdx/Dmd^+	involves: C57BL/10ScSn	MGI:4360111
cx9	Dmd^mdx/Dmd^mdx Mmp9^tm1Tvu/Mmp9^+	B10.Cg-Mmp9^tm1Tvu Dmd^mdx	MGI:4367736
cx10	Dmd^mdx/Dmd^mdx Mmp9^tm1Tvu/Mmp9^tm1Tvu	B10.Cg-Mmp9^tm1Tvu Dmd^mdx	MGI:4367735
cx11	Creb1^tm1.1Berd/Creb1^tm1.1Berd Dmd^mdx/Y	B.Cg-Creb1^tm1.1Berd Dmd^mdx	MGI:5299346
cx12	Dmd^mdx/Dmd^mdx Mamstr^tm1.2Eno/Mamstr^tm1.2Eno	involves: 129 * C57BL/6 * C57BL/10ScSn	MGI:5313412
cx13	Barx2^tm1Rsd/Barx2^tm1Rsd Dmd^mdx/Y	involves: 129 * C57BL/6 * C57BL/10ScSn	MGI:5439173
cx14	Barx2^tm1Rsd/Barx2^tm1Rsd Dmd^mdx/Dmd^mdx	involves: 129 * C57BL/6 * C57BL/10ScSn	MGI:5439179
cx15	Dmd^mdx/Y Tg(DMD*)#Spc/0	involves: 129P2/OlaHsd * C57BL/10ScSn * DBA/2	MGI:6507848
cx16	Dmd^mdx/? Fgf2^tm1Zllr/Fgf2^tm1Zllr Fgf6^tm1Thbr/Fgf6^tm1Thbr	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/10ScSn	MGI:3716189
cx17	Dmd^mdx/Y Dtna^tm1Jrs/Dtna^tm1Jrs Utrn^tm1Jrs/Utrn^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn	MGI:2176891
cx18	Dmd^mdx/Y Utrn^tm1Jrs/Utrn^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn	MGI:5795669
cx19	Dmd^mdx/Dmd^mdx Utrn^tm1Jrs/Utrn^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn	MGI:2176876
cx20	Dmd^mdx/? Fgf2^tm1Zllr/Fgf2^tm1Zllr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn	MGI:3716196
cx21	Dmd^mdx/Dmd^mdx Utrn^tm1Ked/Utrn^tm1Ked	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn * DBA	MGI:2176879
cx22	Ctss^tm1Hap/Ctss^tm1Hap Dmd^mdx/Dmd^mdx	involves: 129S2/SvPas * C57BL/10ScSn	MGI:5779560
cx23	Dmd^mdx/Dmd^mdx Dusp1^tm1Brv/Dusp1^tm1Brv	involves: 129S2/SvPas * C57BL/6 * C57BL/10ScSn	MGI:4940318
cx24	Cav3^tm1Ncnp/Cav3^+ Dmd^mdx/Dmd^mdx	involves: 129S4/SvJae * C57BL/10 * C57BL/10ScSn	MGI:6114163
cx25	Dmd^mdx/Dmd^+ Foxk1^tm1Djg/Foxk1^+	involves: 129S4/SvJae * C57BL/10ScSn	MGI:3655093
cx26	Dmd^mdx/Dmd^+ Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366782
cx27	Dmd^mdx/Y Foxk1^tm1Djg/Foxk1^tm1Djg	involves: 129S4/SvJae * C57BL/10ScSn	MGI:3655090
cx28	Dmd^mdx/Y Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366781
cx29	Dmd^mdx/? Myod1^tm1Jae/Myod1^tm1Jae	involves: 129S4/SvJae * C57BL/10ScSn	MGI:3784305
cx30	Dmd^mdx/Dmd^mdx Foxk1^tm1Djg/Foxk1^tm1Djg	involves: 129S4/SvJae * C57BL/10ScSn	MGI:3655088
cx31	Dag1^tm1.1Swin/Dag1^tm1.1Swin Dmd^mdx/Y	involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn	MGI:5438998
cx32	Dmd^mdx/? Fgf6^tm1Thbr/Fgf6^tm1Thbr	involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn	MGI:3716195
cx33	Dag1^tm1.1Swin/Dag1^tm1.1Swin Dmd^mdx/Dmd^mdx	involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn	MGI:5438997
cx34	Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn	MGI:4361735
cx35	Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn	MGI:4361734
cx36	Dmd^mdx/Y Terc^tm1Rdp/Terc^+	involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL	MGI:4936867
cx37	Dmd^mdx/Y Terc^tm1Rdp/Terc^tm1Rdp	involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL	MGI:4936865
cx38	Dmd^mdx/Y Dtna^tm1Jrs/Dtna^tm1Jrs	involves: 129X1/SvJ * C57BL/10ScSn	MGI:2176892
cx39	Cmah^tm1Avrk/Cmah^tm1Avrk Dmd^mdx/Dmd^mdx	involves: 129X1/SvJ * C57BL/10ScSn	MGI:4889211
cx40	Dmd^mdx/Dmd^mdx Prkdc^scid/Prkdc^scid	involves: BALB/c * C57BL/10ScSn * C57BL/Ka	MGI:5490611
cx41	Dmd^mdx/Y Foxn1^nu/Foxn1^nu	involves: C57BL/10ScSn	MGI:5521335
cx42	Dmd^mdx/Y Mirc37^tm1Boet/Mirc37^tm1Boet	involves: C57BL/10ScSn	MGI:5903046
cx43	Dmd^mdx/Dmd^mdx Tg(ACTA1-SSPN)3.0Rcros/0	involves: C57BL/10ScSn	MGI:5428739
cx44	Dmd^mdx/Dmd^mdx Selenos^tm1.1Sfa/Selenos^+	involves: C57BL/6 * C57BL/10ScSn	MGI:6258417
cx45	Dmd^mdx/Dmd^mdx Snhg15^tm1Nju/Snhg15^tm1Nju	involves: C57BL/6J * C57BL/10ScSn	MGI:6478907
ot46	Dmd^mdx/Y	C57BL/10ScSn-Dmd^mdx	MGI:3798607
ot47	Dmd^mdx/Y	C57BL/10ScSn-Dmd^mdx/J	MGI:3789123
ot48	Dmd^mdx/Y	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366784
ot49	Dmd^mdx/Y	involves: C57BL/10ScSn	MGI:4359635
ot50	Dmd^mdx/?	B6.B10ScSn-Dmd^mdx	MGI:3716194

Genotype
MGI:4359195

hm1

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: C57BL/10ScSn-Dmd^mdx

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

muscle

muscle phenotype ( J:160773 )

♀N • Background Sensitivity: no muscle fibrosis is observed in contrast to the fibrosis observed Dmd^mdx mice on the DBA/2 background

♀N • Background Sensitivity: grip strength scores are similar to wild-type controls in contrast to Dmd^mdx mice on the DBA/2 background

abnormal muscle morphology ( J:7361 )

♀

abnormal atrium myocardial trabeculae morphology ( J:150127 )

♀ • atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

myocardial fiber disarray ( J:150127 )

♀ • cardiac myocyte disorganization

myocardium necrosis ( J:152524 )

♀ • 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

increased quadriceps weight ( J:160773 )

♀ • Background Sensitivity: weight of quadriceps femoris is greater than both wild-type and Dmd^mdx mice on the DBA/2 background

abnormal muscle development ( J:150127 )

♀ • cultured embryonic muscle stem cells from E11.5 to E17.5 exhibit hyperproliferation and apoptosis

♀ • Pax7+ skeletal muscle stem cell population is reduced and disorganized at E17.5

abnormal myotube morphology ( J:150127 )

♀ • myotube alignment is disrupted early in myogenesis

♀ • muscles exhibit a small reduction in myotube number at E13.5-E17.5

♀ • myotubes are hypotrophic in E13.5-E17.5 muscles

♀ • myotube width varies more in E13.5-E17.5 muscles than in wild-type muscle

♀ • misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

♀ • myonuclei are more frequently located centrally and slightly further apart in the myotube at E15.5

♀ • only central nuclei (not peripheral) are present in E15.5 muscles

♀ • myotube defects occur earlier in intercostals at E13.5 than proximal limb muscles at E15.5

dilated sarcoplasmic reticulum ( J:7361 )

♀

abnormal skeletal muscle fiber morphology ( J:7361 , J:152524 )

♀ • development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina (J:7361)

♀ • the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned (J:7361)

♀ • myopathic lesions in skeletal muscle are found by 22 days of age and are characterized by widespread loss of sarcoplasmic structure, vacuolation, and eosinophilia (J:152524)

♀ • myotubes indicative of muscle regeneration are found by 22 days of age and by 31 days of age almost all muscles have numerous myotubes (J:152524)

increased variability of skeletal muscle fiber size ( J:7361 )

♀ • variable muscle fiber size; progressive starting at 3 weeks of age

centrally nucleated skeletal muscle fibers ( J:150127 , J:152524 )

♀ • only central nuclei (not peripheral) are present in E15.5 muscles (J:150127)

♀ • 25% of fibers have non-peripheral nuclei at 26 days of age and 53% at 100 to 303 days of age (J:152524)

increased skeletal muscle fiber number ( J:160773 )

♀ • Background Sensitivity: total number of myofibers is greater than total number of myofibers found in Dmd^mdx mice on the DBA/2 background

abnormal intercostal muscle morphology ( J:150127 )

♀ • misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

♀ • intercostal muscle fibers are distributed more sparsely at E17.5 and fetuses have reduced intercostal muscle fiber densities

♀ • 37.5% depletion of intercostal myotubes by E17.5

increased skeletal muscle mass ( J:160773 )

♀ • Background Sensitivity: in comparison to Dmd^mdx mice on the DBA/2 background

increased skeletal muscle weight ( J:160773 )

♀ • Background Sensitivity: weights of tibialis anterior and gastrocnemius muscles are greater than both wild-type and Dmd^mdx mice on the DBA/2 background

skeletal muscle fibrosis ( J:7361 )

♀ • exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis ( J:7361 )

♀ • progressive starting at 9 weeks of age

skeletal muscle fiber necrosis ( J:152524 )

♀

dystrophic muscle ( J:7361 )

♀

muscle degeneration ( J:7361 )

♀ • progressive starting at 3 weeks of age

muscular atrophy ( J:7361 )

♀ • progressive starting at 3 weeks of age

myopathy ( J:7361 )

♀ • progressive degenerative myopathy; increased severity with age

reproductive system

reduced female fertility ( J:7361 )

♀ • slight reduction in fertility

adipose tissue

adipose tissue phenotype ( J:160773 )

♀N • Background Sensitivity: no fat accumulation is observed in contrast to Dmd^mdx mice on the DBA/2 background

behavior/neurological

decreased aerobic running capacity ( J:160773 )

♀ • Background Sensitivity: mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

cardiovascular system

myocardial fiber disarray ( J:150127 )

♀ • cardiac myocyte disorganization

myocardium necrosis ( J:152524 )

♀ • 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

abnormal heart atrium morphology ( J:150127 )

♀ • distention or separation of the myocardial and endocardial cell layers of the atria occurs at E17.5

abnormal atrium myocardial trabeculae morphology ( J:150127 )

♀ • atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

thick ventricular wall ( J:150127 )

♀

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:18080 , J:152524 )

♀N • serum T4 and thyroid stimulating hormone are normal (J:18080)

♀N • serum pyruvate kinase activity is normal (J:152524)

decreased aerobic running capacity ( J:160773 )

♀ • Background Sensitivity: mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

increased circulating creatine kinase level ( J:7361 , J:18080 , J:152524 )

♀ • exhibit elevated blood levels of creatine kinase (J:7361)

♀ • serum creatine kinase is elevated at 2 months of age (J:18080)

♀ • serum creatine kinase activity is elevated between 12 and 200 days of age (J:152524)

abnormal circulating pyruvate kinase level ( J:7361 )

♀ • exhibit elevated blood levels of pyruvate kinase

increased growth hormone level ( J:18080 )

♀ • pituitary growth hormone levels is slightly higher than normal in 8 to 10 month old females

endocrine/exocrine glands

abnormal corticotroph morphology ( J:18080 )

♀ • some corticotrophs have enlarged golgi stacks

increased somatotroph cell size ( J:18080 )

♀ • dilation of the rough endoplasmic reticulum, enlarged golgi apparatus, and the presence of many dense secretory granules of homogeneous size are characteristics of the hypertrophic somatotrophs of homozygotes

nervous system

abnormal corticotroph morphology ( J:18080 )

♀ • some corticotrophs have enlarged golgi stacks

increased somatotroph cell size ( J:18080 )

♀ • dilation of the rough endoplasmic reticulum, enlarged golgi apparatus, and the presence of many dense secretory granules of homogeneous size are characteristics of the hypertrophic somatotrophs of homozygotes

limbs/digits/tail

increased quadriceps weight ( J:160773 )

♀ • Background Sensitivity: weight of quadriceps femoris is greater than both wild-type and Dmd^mdx mice on the DBA/2 background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:150127

Genotype
MGI:3621491

hm2

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: C57BL/10ScSn-Dmd^mdx/J

muscle

abnormal muscle morphology ( J:7361 )

♀

dilated sarcoplasmic reticulum ( J:7361 )

♀

abnormal skeletal muscle fiber morphology ( J:7361 )

♀ • development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina

♀ • the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

increased skeletal muscle fiber diameter ( J:226314 )

♀ • tibialis anterior muscle fibers are increased in diameter (1500 m²) as compared to C57BL/10ScSn mice (375-750 m²)

increased variability of skeletal muscle fiber size ( J:7361 )

♀ • variable muscle fiber size; progressive starting at 3 weeks of age

centrally nucleated skeletal muscle fibers ( J:226314 )

♀ • mice exhibit an increased number of centrally nucleated fibers

♀ • Background Sensitivity: increase is less than in Dmd^mdx mice on the DBA/2J background than in mice on the C57BL/10ScSn background

♀ • Background Sensitivity: myonuclei are predominantly centrally located in contrast to juxtasarcolemmal position in mice on the DBA/2J background

increased skeletal muscle mass ( J:226314 )

♀ • increase in muscle mass in gastrocnemius, tibialis anterior and quadriceps as compared to controls

♀ • increased muscle mass in EDL as compared to C57BL/10ScSn control at 28 and 52 weeks of age

♀ • Background Sensitivity: increased muscle mass in EDL as compared to Dmd^mdx mice on the DBA/2J background at 7, 28 and 52 weeks of age

skeletal muscle hypertrophy ( J:226314 )

♀ • muscle hypertrophy observed in gastrocnemius, tibialis anterior and quadriceps

♀ • Background Sensitivity: hypertrophy is not observed in Dmd^mdx mice on the DBA/2J background

skeletal muscle fibrosis ( J:7361 )

♀ • exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis ( J:7361 )

♀ • progressive starting at 9 weeks of age

calcified muscle ( J:226314 )

♀ • calcium deposits are observed in quadriceps at 52 weeks of age

♀ • Background Sensitivity: however, Dmd^mdx mice on the DBA/2J background develop calcium deposits by 7 weeks of age

dystrophic muscle ( J:7361 , J:226314 )

♀ (J:7361)

♀ • onset of muscular dystrophy is earlier and more severe in Dmd^mdx mice on the DBA/2J background (J:226314)

muscle degeneration ( J:7361 )

♀ • progressive starting at 3 weeks of age

skeletal muscle degeneration ( J:226314 )

♀ • lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

♀ • increased uptake of Evans blue dye, a measure of muscle damage, as compared to C57BL/10ScSn controls at 8 weeks of age

♀ • Background Sensitivity: however, uptake is lower than in Dmd^mdx mice on the DBA/2J background

muscular atrophy ( J:7361 )

♀ • progressive starting at 3 weeks of age

abnormal muscle physiology ( J:3666 )

♀ • increased intracellular sodium concentration in muscle; increased severity with age

decreased cardiac muscle contractility ( J:226314 )

♀ • lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

♀ • Background Sensitivity: ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age

cardiomyopathy ( J:226314 )

♀ • cardiomyopathy is observed at 28 weeks of age

♀ • Background Sensitivity: cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

myositis ( J:226314 )

♀ • hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

♀ • inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

♀ • Background Sensitivity: unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

impaired skeletal muscle contractility ( J:226314 )

♀ • decrease in specific force generation in extensor digitorum longus (EDL) as compared to C57BL/10ScSn controls at 28 and 52 weeks of age

♀ • Background Sensitivity: increase in specific and maximum force generation in EDL as compared to Dmd^mdx mice on the DBA/2J background

abnormal skeletal muscle regeneration ( J:226314 )

♀ • lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

myopathy ( J:7361 )

♀ • progressive degenerative myopathy; increased severity with age

reproductive system

reduced female fertility ( J:7361 )

♀ • slight reduction in fertility

cardiovascular system

cardiovascular system phenotype ( J:226314 )

♀N • Background Sensitivity: mice do not exhibit inflammation in cardiac tissue in contrast to Dmd^mdx mice on the DBA/2J background

enlarged heart ( J:226314 )

♀ • enlarged heart as compared to C57BL/10ScSn controls

♀ • enlargement is significant at 52 weeks of age

decreased cardiac output ( J:226314 )

♀

decreased cardiac stroke volume ( J:226314 )

♀

decreased cardiac muscle contractility ( J:226314 )

♀ • lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

♀ • Background Sensitivity: ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age

cardiomyopathy ( J:226314 )

♀ • cardiomyopathy is observed at 28 weeks of age

♀ • Background Sensitivity: cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

growth/size/body

enlarged heart ( J:226314 )

♀ • enlarged heart as compared to C57BL/10ScSn controls

♀ • enlargement is significant at 52 weeks of age

increased body size ( J:226314 )

♀ • mice have increased body mass as compared to C57BL/10ScSn controls

♀ • Background Sensitivity: mice have increased body mass as compared to Dmd^mdx mice on the DBA/2J background at 28 weeks

hearing/vestibular/ear

abnormal auditory brainstem response waveform shape ( J:105938 )

♀ • prolonged brainstem auditory evoked potential peak and interpeak latencies after noise exposure

increased or absent threshold for auditory brainstem response ( J:105938 )

♀ • significantly increased hearing threshold after noise exposure

increased susceptibility to noise-induced hearing loss ( J:105938 )

♀ • daily exposure to noise for 1 month increased hearing threshold and prolonged brainstem auditory evoked potential peak and interpeak latencies

homeostasis/metabolism

increased circulating creatine kinase level ( J:7361 , J:226314 )

♀ • exhibit elevated blood levels of creatine kinase (J:7361)

♀ • elevated levels of serum creatine kinase as compared to C57BL/10ScSn controls at 24 and 28 weeks (J:226314)

♀ • Background Sensitivity: levels are higher than Dmd^mdx mice on the DBA/2J background at 24 weeks (J:226314)

abnormal circulating pyruvate kinase level ( J:7361 )

♀ • exhibit elevated blood levels of pyruvate kinase

increased creatine kinase activity ( J:226314 )

♀ • increased creatine kinase activity as compared to C57BL/10ScSn controls at 24 and 28 weeks

♀ • Background Sensitivity: activity is higher than Dmd^mdx mice on the DBA/2J background at 24 weeks

immune system

increased interferon-gamma secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased interleukin-12 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased interleukin-2 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks and 2 years of age

increased interleukin-4 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks, 4 weeks, and 2 years of age

increased interleukin-6 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased tumor necrosis factor secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

myositis ( J:226314 )

♀ • hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

♀ • inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

♀ • Background Sensitivity: unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

behavior/neurological

impaired coordination ( J:106640 )

♀ • performance is similar to that observed in double knockouts

abnormal grip strength ( J:106640 )

♀ • performance is similar to that observed in double knockouts

decreased grip strength ( J:226314 )

♀ • reduced forelimb and hindlimb grip strength beginning at 6 weeks as compared to controls

♀ • Background Sensitivity: forelimb grip strength is less than Dmd^mdx mice on the DBA/2J background at 28 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:7361

Genotype
MGI:5688354

hm3

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: D2.B10-Dmd^mdx

adipose tissue

increased total body fat amount ( J:160773 )

• Background Sensitivity: increased fat accumulation in comparison to Dmd^mdx mice on the C57BL/10 background

behavior/neurological

decreased aerobic running capacity ( J:160773 )

• Background Sensitivity: mice run shorter distances than wild-type and Dmd^mdx mice on the C57BL/10 background

• mice run 45% (male) and 56% (female) shorter distances than wild-type

• maximum running speed in both males and females is less than in wild-type mice

growth/size/body

decreased body weight ( J:160773 )

• decreased body weight as compared to wild-type

homeostasis/metabolism

decreased aerobic running capacity ( J:160773 )

• Background Sensitivity: mice run shorter distances than wild-type and Dmd^mdx mice on the C57BL/10 background

• mice run 45% (male) and 56% (female) shorter distances than wild-type

• maximum running speed in both males and females is less than in wild-type mice

muscle

decreased quadriceps weight ( J:160773 )

• Background Sensitivity: weight of quadriceps femoris is less than both wild-type and Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle fiber number ( J:160773 )

• Background Sensitivity: decreased number of total myofibers in comparison to Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle mass ( J:160773 )

• Background Sensitivity: in comparison to Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle weight ( J:160773 )

• Background Sensitivity: weights of tibialis anterior and gastrocnemius muscles are less than both wild-type and Dmd^mdx mice on the C57BL/10 background

skeletal muscle fibrosis ( J:160773 )

• Background Sensitivity: increased fibrosis volume in quadriceps femoris as compared to Dmd^mdx mice on the C57BL/10 background

muscle weakness ( J:160773 )

• Background Sensitivity: mice exhibit lower grip strength test scores than wild-type mice and Dmd^mdx mice on the C57BL/10 background

limbs/digits/tail

decreased quadriceps weight ( J:160773 )

• Background Sensitivity: weight of quadriceps femoris is less than both wild-type and Dmd^mdx mice on the C57BL/10 background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:160773

Genotype
MGI:5697652

hm4

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: D2.B10-Dmd^mdx/J

muscle

cardiac muscle degeneration ( J:226314 )

decreased cardiac muscle contractility ( J:226314 )

• lower ejection fraction and shortening fraction than DBA/2J controls at 28 and 52 weeks of age

• Background Sensitivity: ejection fraction and shortening fraction is lower than in Dmd^mdx mice on C57BL/10ScSn background at 28 weeks of age

cardiomyopathy ( J:226314 )

• cardiomyopathy is observed at 7 weeks of age in mice on the DBA/2J background

• Background Sensitivity: cardiomyopathy is observed at 28 weeks of age in Dmd^mdx mice on the C57BL/10ScSn background

myositis ( J:226314 )

• forelimb and hindlimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

• inflammation in the forelimb is still observed at 52 weeks of age

• inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

• Background Sensitivity: forelimb inflammation at 52 weeks is not observed in mice on on the C57BL/10ScSn background

abnormal skeletal muscle fiber morphology ( J:226314 )

♂ • high incidence of primary and complex branching in myofibers from extensor digitorum longus (EDL) in 12 week old male mice

decreased skeletal muscle fiber size ( J:226314 )

• increase in average number of nuclei per myofiber and decreased F-actin content from EDL at 12 weeks of age

• decrease in myonuclear domain from EDL at 12 weeks of age

• increased number of small fibers and smaller number of normal sized fibers

decreased skeletal muscle fiber diameter ( J:226314 )

• tibialis anterior muscle fibers are reduced in diameter (375 m²) as compared to DBA/2J mice (375-750 m²)

centrally nucleated skeletal muscle fibers ( J:226314 )

• mice exhibit an increased number of centrally nucleated fibers

• myonuclei are predominantly located in juxtasarcolemmal position on the DBA/2J background

• Background Sensitivity: increase is less on the DBA/2J background than on the C57BL/10ScSn background

• Background Sensitivity: myonuclei are predominantly centrally located on the C57BL/10ScSn background

decreased skeletal muscle mass ( J:226314 )

• loss of muscle mass in gastrocnemius, tibialis anterior and quadriceps as compared to controls

• reduced muscle mass in extensor digitorum longus (EDL) as compared to DBA/2J at 28 and 52 weeks of age

• Background Sensitivity: reduced muscle mass in EDL as compared to Dmd^mdx mice on C57BL/10ScSn background at 7, 28 and 52 weeks of age

skeletal muscle atrophy ( J:226314 )

• muscle atrophy is observed in mice on the DBA/2J background

• Background Sensitivity: however, muscle hypertrophy is observed in Dmd^mdx mice on the C57BL/10ScSn background

skeletal muscle fiber atrophy ( J:226314 )

skeletal muscle degeneration ( J:226314 )

• lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

• increased uptake of Evans blue dye, a measure of muscle damage, as compared to DBA/2J controls at 8 weeks of age

• Background Sensitivity: uptake is higher than in Dmd^mdx mice on the C57BL/10ScSn background

calcified muscle ( J:226314 )

• calcifications in quadriceps, heart, diaphragm and epicardium of heart at 7 weeks of age

• Background Sensitivity: Dmd^mdx mice on the C57BL/10ScSn background did not exhibit calcifications until 52 weeks of age

dystrophic muscle ( J:226314 )

• Background Sensitivity: onset of muscular dystrophy is later and less severe in Dmd^mdx mice on on the C57BL/10ScSn background

impaired skeletal muscle contractility ( J:226314 )

• decrease in specific and maximal force generation in EDL at 7, 28 and 52 weeks as compared to DBA/2J controls

• Background Sensitivity: decrease in specific and maximal force generation in EDL at 7 and 28 weeks as compared to Dmd^mdx mice on C57BL/10ScSn background

abnormal skeletal muscle regeneration ( J:226314 )

• lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

cardiovascular system

cardiac muscle degeneration ( J:226314 )

dystrophic cardiac calcinosis ( J:226314 )

• calcifications in quadriceps, heart, diaphragm and epicardium of heart at 7 weeks of age

• Background Sensitivity: Dmd^mdx mice on the C57BL/10ScSn background did not exhibit calcifications until 52 weeks of age

decreased cardiac output ( J:226314 )

decreased cardiac stroke volume ( J:226314 )

• decreased left ventricular (stroke) volume

decreased cardiac muscle contractility ( J:226314 )

• lower ejection fraction and shortening fraction than DBA/2J controls at 28 and 52 weeks of age

• Background Sensitivity: ejection fraction and shortening fraction is lower than in Dmd^mdx mice on C57BL/10ScSn background at 28 weeks of age

cardiomyopathy ( J:226314 )

• cardiomyopathy is observed at 7 weeks of age in mice on the DBA/2J background

• Background Sensitivity: cardiomyopathy is observed at 28 weeks of age in Dmd^mdx mice on the C57BL/10ScSn background

heart inflammation ( J:226314 )

• inflammation within cardiac tissue is observed by 7 weeks of age

• Background Sensitivity: inflammation is not observed in in Dmd^mdx mice on the C57BL/10ScSn background

growth/size/body

decreased body size ( J:226314 )

• mice have reduced body mass as compared to DBA/2J controls

• Background Sensitivity: Dmd^mdx mice on the DBA/2J background have reduced body mass as compared to mice on the C57BL/10ScSn background at 28 weeks

homeostasis/metabolism

increased circulating creatine kinase level ( J:226314 )

• elevated levels of serum creatine kinase as compared to DBA/2J controls at 24 and 28 weeks

• Background Sensitivity: levels are lower at 24 weeks as compared to Dmd^mdx mice on the C57BL/10ScSn background

increased creatine kinase activity ( J:226314 )

• increased creatine kinase activity as compared to DBA/2J controls at 24 and 28 weeks

• Background Sensitivity: activity is lower at 24 weeks as compared to Dmd^mdx mice on the C57BL/10ScSn background

immune system

heart inflammation ( J:226314 )

• inflammation within cardiac tissue is observed by 7 weeks of age

• Background Sensitivity: inflammation is not observed in in Dmd^mdx mice on the C57BL/10ScSn background

myositis ( J:226314 )

• forelimb and hindlimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

• inflammation in the forelimb is still observed at 52 weeks of age

• inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

• Background Sensitivity: forelimb inflammation at 52 weeks is not observed in mice on on the C57BL/10ScSn background

behavior/neurological

decreased grip strength ( J:226314 )

• reduced forelimb grip strength at 12 weeks and 24 weeks as compared to controls

• reduced hindlimb grip strength at 24 weeks, as compared to controls, however, gap closes by 52 weeks

• Background Sensitivity: forelimb grip strength at 28 weeks is higher than grip strength in Dmd^mdx mice on C57BL/10ScSn background, but still less than controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:226314

Genotype
MGI:5490615

hm5

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: involves: BALB/c * C57BL/10ScSn * C57BL/Ka

homeostasis/metabolism

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• lower endurance on treadmill than Prkdc^scid Dmd^mdx double mutants

increased transforming growth factor beta level ( J:125527 )

• costal diaphragm (DIA) has higher quantity of active TGFB1 in comparison to Prkdc^scid Dmd^mdx double mutants although total quantity is similar

• tibialis anterior (TA) and quadricepts (QA) muscles have a higher content of total TGB1 in comparison to Prkdc^scid Dmd^mdx double mutants

muscle

increased skeletal muscle fiber diameter ( J:125527 )

• area of muscle fibers is 1500-1700 um² and coefficient of variance is 55-65

centrally nucleated skeletal muscle fibers ( J:125527 )

• small, centrally nucleated, regenerating muscle fibers are found in 2 and 12 month old mice

• 40-45% of muscle fibers exhibit centrally located nuclei

skeletal muscle fiber degeneration ( J:125527 )

• degenerating muscle fibers are found in 2 and 12 month old mice

skeletal muscle fibrosis ( J:125527 )

• high rate of fibrosis is observed in aged 12 month old mice

impaired skeletal muscle contractility ( J:125527 )

• loss of normalized tetanic force is observed in 2 and 12 month old mice

skeleton

abnormal vertebral column morphology ( J:125527 )

• progressive spinal deformity

behavior/neurological

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• lower endurance on treadmill than Prkdc^scid Dmd^mdx double mutants

Genotype
MGI:2654139

hm6

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: involves: C57BL/10ScSn

growth/size/body

abnormal scalene muscle morphology ( J:152891 )

♀ • the anterior scalene muscle at 1 to 1.5 years of age show dystrophic changes similar to those of the diaphragm at 6 months of age

muscle

dilated sarcoplasmic reticulum ( J:152892 )

♀ • from 2 weeks of age in both type 1 and 2 fibers of the extensor digitorum longus and soleus

abnormal skeletal muscle morphology ( J:152892 )

♀ • regenerating fibers, with central nuclei, are most abundant around 35 to 39 days of age when they are approximately 30% of the extensor digitorum longus and 50% of the soleus

abnormal scalene muscle morphology ( J:152891 )

♀ • the anterior scalene muscle at 1 to 1.5 years of age show dystrophic changes similar to those of the diaphragm at 6 months of age

abnormal skeletal muscle fiber morphology ( J:152525 , J:152749 , J:152892 )

♀ • at 15 days of age necrotic fibers are found, occassionally in clusters, at 20 days of age necrotic fibers are numerous as are groups of regenerating fibers with internally placed nuclei, necrotic fibers are most numerous between 30 and 60 days of age and gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but there is almost no fibrous tissue proliferation or adipose tissue replacement (J:152525)

♀ • the extensor digitorum longus, but not the soleus, at 32 weeks of age has a greater proportion of fast-twitch-oxidative-glycolytic fibers and a smaller proportion of fast-twitch-glycolytic fibers than controls (J:152749)

♀ • electron microscopy shows an accumulation of small pools of non-membrane-bound glycogen from 14 days of age on in both type 1 and type 2 fibers, and membrane-bound vacuoles of variable size and form with finely granular contents are found beginning at 2 weeks of age in the type 1 fibers of the soleus but not extensor digitorum longus (J:152892)

increased skeletal muscle fiber diameter ( J:19034 , J:152749 )

♀ • although the number of fibers is normal, the cross-sectional area of the fibers of the tibialis anterior is larger than normal at 3 and 6 months of age (J:19034)

♀ • at 32 weeks of age in the soleus fast-twitch-oxidative-glycolytic fibers have a larger cross-sectional area than those of controls (J:152749)

♀ • at 32 weeks of age in the extensor digitorum longus muscle both the slow-twitch-oxidative and fast-twitch-glycolytic fibers have a larger cross-sectional area than those of controls (J:152749)

centrally nucleated skeletal muscle fibers ( J:19034 , J:152525 )

♀ • peripherally nucleated fibers replace the normal fibers in the tibialis anterior, extensor digitorum longus, plantaris, and soleus in a progressive manner, reaching a plateau of 80-90% of fibers at 26 weeks of age (J:19034)

♀ (J:152525)

abnormal diaphragm morphology ( J:152891 )

♀ • unlike skeletal muscle, the diaphragm undergoes progressive degeneration without regeneration such that, although at 30 days of age foci of myofiber degeneration, necrosis, mineralization, and regeneration are present but not extensive, at 6 months of age the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibers are ensheathed in dense collagenous tissue with most having architectural aberrations

♀ • at 16 months of age there are twice normal levels of slow myosin in the diaphragm, a decrease in isometric force generation, and a shortened fiber length

♀ • at 1.5 years of age the diaphragm is found to have significantly reduced passive stretch capacity although overt respiratory compromise is not found in aging mutants

abnormal intercostal muscle morphology ( J:152891 )

♀ • the intercostal muscles at 1 to 1.5 years of age have dystrophic changes similar to those of the diaphragm at 6 months of age

increased skeletal muscle mass ( J:19034 )

♀ • the cross-sectional area and wet weight of the tibialis anterior is greater than normal by 10 weeks of age

skeletal muscle hypertrophy ( J:19034 )

♀ • detectable up to 12 months of age but not at 15 months of age, at which point muscle fibers appear atrophied and extensively split

skeletal muscle endomysial fibrosis ( J:19034 )

♀ • found with age in the soleus and plantaris

skeletal muscle necrosis ( J:152892 )

♀ • by 28 days of age necrosis and phagocytosis, with rounded off and swollen mitochondria in the necrotic fibers, is widespread, but is rare at 21 days of age

skeletal muscle fiber necrosis ( J:19034 , J:152525 , J:152892 )

♀ • scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on (J:19034)

♀ (J:152525)

♀ • although younger homozygotes do not have fat or fibrous connective tissue in the skeletal muscles, by 270 days of age some fibrous connective tissue is found (J:152892)

abnormal muscle physiology ( J:152750 )

♀ • in skeletal muscle fibers myosin magnesium-ATPase activity is higher than normal, myosin B ATPase activity is higher than normal in low free calcium concentrations, and rapid phosphate liberation by magnesium-ATPase is lower than normal

abnormal skeletal muscle satellite cell proliferation ( J:152892 )

♀ • satellite cell mitosis is found at 14 days of age and by 28 days increased satellite cells are found in healthy appearing fibers but frequently adjacent to necrotic fibers

abnormal muscle contractility ( J:152525 )

♀ • scattered hypercontracted fibers are found by electron microscopy at 10 days of age

abnormal muscle electrophysiology ( J:142492 )

♀ • at 23 degrees hemidiaphragm preparations show lower than normal resting membrane potentials and insertion of a glass microelectrode into a single muscle fiber results in repetitive bursts of muscle action potentials in 30 to 50% of fibers, while at 37 degrees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal

abnormal muscle tone ( J:152749 )

♀ • at 4 weeks of age the soleus muscle has decreased twitch and tetanus tension compared with controls, but this is normal by 32 weeks of age

♀ • at 3 and 32 weeks of age the extensor digitorum longus muscle has decreased twitch and tetanus tension and faster time-to-peak twitch tension compared with controls and the maximum velocity of unloaded shortening is also decreased at 32 weeks of age

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:20768 )

♀ • injection of the gastrocnemius muscle with chlorpromazine results in a less destruction of calmitine than in controls (20% versus 40%) and has less of an impact on calcium binding to calmitine

vision/eye

nuclear cataract ( J:142492 )

♀ • nuclear opacity of the lens is found at 1 day of age

anterior subcapsular cataract ( J:142492 )

♀ • a slight anterior subcapsular opacity is seen at 4 days of age, which spreads anteriorly such that at 150 days of age there is complete anterior subcapsular opacity in addition to the nuclear opacity

nervous system

nervous system phenotype ( J:121319 )

♀N • at 8 weeks of age miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents, and the number of acetylcholine receptors at the postsynaptic membrane are all normal

abnormal neuromuscular synapse morphology ( J:121319 )

♀ • although the nerve terminal innervation of epitronchleoanconeus muscle is normal, the terminal architecture of regenerated muscle fibers, those with central nuclei, are more complex than normal with an increase in the number of fine terminal aborizations, many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcholinesterase staining in close association

♀ • electron microscopy shows that neuromuscular junction postsynaptic membranes are variably simplified with a reduction in the number of secondary synaptic folds

cellular

abnormal skeletal muscle satellite cell proliferation ( J:152892 )

♀ • satellite cell mitosis is found at 14 days of age and by 28 days increased satellite cells are found in healthy appearing fibers but frequently adjacent to necrotic fibers

Genotype
MGI:4366785

ht7

• Allelic Composition: Dmd^mdx/Dmd⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♀ • mice show isolated dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♀ • moderate elevation of pyruvate kinase levels is detectable by P21

Genotype
MGI:4360111

ht8

• Allelic Composition: Dmd^mdx/Dmd⁺
• Genetic Background: involves: C57BL/10ScSn

muscle

abnormal skeletal muscle fiber morphology ( J:121251 )

♀ • consistent with X-inactivation, heterozygous females have a mosaic absence of dystrophin, but this diminishes with age such that at 10 days of age 37% of the fibers in a cross section of the quadriceps lack dystrophin staining, at 35 days of age only 18% of fibers lack dystrophin, and by 60 days of age only 4% lack dystrophin, in extraocular muscles the proportions of dystrophin expressing and non-expressing fibers is similar and in cardiac ventricular muscle approximately 30% of fibers lack dystrophin at 10 days of age, and 28% lack dystrophin at 60 days of age

♀ • unlike hemizygotes or homozygotes, necrosis of muscle fibers is very rare

Genotype
MGI:4367736

cx9

• Allelic Composition: Dmd^mdx/Dmd^mdx; Mmp9^tm1Tvu/Mmp9⁺
• Genetic Background: B10.Cg-Mmp9^tm1Tvu Dmd^mdx

muscle

abnormal muscle morphology ( J:150030 )

♀ • mice exhibit improved muscle and sarcolemmal structure, more uniform fiber diameter, reduced inflammatory cell between adjacent fibers, and decreased necrosis and fibrosis compared with Dmd^mdx homozygotes

abnormal muscle physiology ( J:150030 )

♀ • mice exhibit higher muscle force production compared with Dmd^mdx homozygotes

enhanced skeletal muscle regeneration ( J:150030 )

♀ • myofiber regeneration is increased compared to in Dmd^mdx homozygotes

immune system

decreased macrophage cell number ( J:150030 )

♀ • fewer macrophages accumulate in the muscles compared to in Dmd^mdx homozygotes

hematopoietic system

decreased macrophage cell number ( J:150030 )

♀ • fewer macrophages accumulate in the muscles compared to in Dmd^mdx homozygotes

Genotype
MGI:4367735

cx10

• Allelic Composition: Dmd^mdx/Dmd^mdx; Mmp9^tm1Tvu/Mmp9^tm1Tvu
• Genetic Background: B10.Cg-Mmp9^tm1Tvu Dmd^mdx

muscle

abnormal muscle morphology ( J:150030 )

♀ • mice exhibit improved muscle and sarcolemmal structure, more uniform fiber diameter, reduced inflammatory cell between adjacent fibers, and decreased necrosis and fibrosis compared with Dmd^mdx homozygotes

enhanced skeletal muscle regeneration ( J:150030 )

♀ • myofiber regeneration is increased compared to in Dmd^mdx homozygotes

immune system

decreased macrophage cell number ( J:150030 )

♀ • fewer macrophages accumulate in the muscles compared to in Dmd^mdx homozygotes

hematopoietic system

decreased macrophage cell number ( J:150030 )

♀ • fewer macrophages accumulate in the muscles compared to in Dmd^mdx homozygotes

Genotype
MGI:5299346

cx11

• Allelic Composition: Creb1^tm1.1Berd/Creb1^tm1.1Berd; Dmd^mdx/Y
• Genetic Background: B.Cg-Creb1^tm1.1Berd Dmd^mdx

muscle

skeletal muscle degeneration ( J:177923 )

♂ • muscle degeneration proceeds as in Dmd^mdx mice

enhanced skeletal muscle regeneration ( J:177923 )

♂ • muscle regeneration is increased compared to in Dmd^mdx mice

Genotype
MGI:5313412

cx12

• Allelic Composition: Dmd^mdx/Dmd^mdx; Mamstr^tm1.2Eno/Mamstr^tm1.2Eno
• Genetic Background: involves: 129 * C57BL/6 * C57BL/10ScSn

muscle

abnormal skeletal muscle satellite cell proliferation ( J:179880 )

♀ • hyperproliferative in culture

decreased skeletal muscle weight ( J:179880 )

♀ • at 4 and 6 weeks of age compared to mice homozygous for Dmd^mdx alone

skeletal muscle fibrosis ( J:179880 )

♀ • severe muscle damage and increased fibrosis

muscle degeneration ( J:179880 )

♀ • severe muscle damage and increased fibrosis

growth/size/body

decreased body weight ( J:179880 )

♀ • at 4 and 6 weeks of age compared to mice homozygous for Dmd^mdx alone

cellular

abnormal skeletal muscle satellite cell proliferation ( J:179880 )

♀ • hyperproliferative in culture

Genotype
MGI:5439173

cx13

• Allelic Composition: Barx2^tm1Rsd/Barx2^tm1Rsd; Dmd^mdx/Y
• Genetic Background: involves: 129 * C57BL/6 * C57BL/10ScSn

mortality/aging

postnatal lethality, incomplete penetrance ( J:187799 )

♂ • mutants are under-represented at weaning age

growth/size/body

decreased body size ( J:187799 )

♂ • mutants are about 30% smaller than single Dmd mutants at 4 weeks of age; organs are reduced proportionately

behavior/neurological

abnormal gait ( J:187799 )

♂ • mutants become progressively less ambulatory with a waddling gait

♂ • gait abnormalities appear earlier and are more severe than in single Barx2 mutants

decreased locomotor activity ( J:187799 )

♂ • mutants become progressively less ambulatory

muscle

increased variability of skeletal muscle fiber size ( J:187799 )

♂ • organization of tibialis anterior muscle is extremely aberrant with greater variability in myofiber size and fewer central nuclei releative to muscle from single Dmd mutants

♂ • soleus muscles show greater variability in myofiber size and shape compared to muscle from single Dmd mutants

skeletal muscle fiber necrosis ( J:187799 )

♂

decreased muscle weight ( J:187799 )

♂ • tibialis anterior muscle weighs on average 50% less than in single Dmd mutants, indicating muscle wasting

abnormal diaphragm morphology ( J:187799 )

♂ • at 12 months of age, diaphragms show a greater instance of focal myofiber necrosis and necrotic myofibers undergoing myophagocytosis and more fibrosis compared to single Dmd mutants

thin diaphragm muscle ( J:187799 )

♂ • diaphragm muscles at 6 months of age are much thinner than in single Dmd mutants and show more frequent rounded opaque fibers often with clear vacuoles, indicating hypercontracted atrophic fibers

skeletal muscle fibrosis ( J:187799 )

♂ • soleus muscles show more endomysial and perimysial fibrosis compared to muscle from single Dmd mutants

♂ • diaphragms show more fibrosis than single Dmd mutants

skeletal muscle endomysial fibrosis ( J:187799 )

♂ • in soleus muscles

impaired skeletal muscle regeneration ( J:187799 )

♂ • tibialis anterior muscle shows fewer central nuclei relative to muscle from single Dmd mutants, indicating reduction in repair of muscle damage

progressive muscle weakness ( J:187799 )

♂ • mutants become progressively weak

skeleton

kyphosis ( J:187799 )

♂ • mutants develop spine deformation resembling kyphosis by 6 months of age

♂ • spine deformation appears earlier and is more severe than in single Barx2 mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:187799

Genotype
MGI:5439179

cx14

• Allelic Composition: Barx2^tm1Rsd/Barx2^tm1Rsd; Dmd^mdx/Dmd^mdx
• Genetic Background: involves: 129 * C57BL/6 * C57BL/10ScSn

mortality/aging

postnatal lethality, incomplete penetrance ( J:187799 )

♀ • mutants are under-represented at weaning age

growth/size/body

decreased body size ( J:187799 )

♀ • mutants are about 30% smaller than single Dmd mutants at 4 weeks of age; organs are reduced proportionately

behavior/neurological

abnormal gait ( J:187799 )

♀ • mutants become progressively less ambulatory with a waddling gait

♀ • gait abnormalities appear earlier and are more severe than in single Barx2 mutants

decreased locomotor activity ( J:187799 )

♀ • mutants become progressively less ambulatory

muscle

increased variability of skeletal muscle fiber size ( J:187799 )

♀ • organization of tibialis anterior muscle is extremely aberrant with greater variability in myofiber size and fewer central nuclei releative to muscle from single Dmd mutants

♀ • soleus muscles show greater variability in myofiber size and shape compared to muscle from single Dmd mutants

skeletal muscle fiber necrosis ( J:187799 )

♀

decreased muscle weight ( J:187799 )

♀ • tibialis anterior muscle weighs on average 50% less than in single Dmd mutants, indicating muscle wasting

abnormal diaphragm morphology ( J:187799 )

♀ • at 12 months of age, diaphragms show a greater instance of focal myofiber necrosis and necrotic myofibers undergoing myophagocytosis and more fibrosis compared to single Dmd mutants

thin diaphragm muscle ( J:187799 )

♀ • diaphragm muscles at 6 months of age are much thinner than in single Dmd mutants and show more frequent rounded opaque fibers often with clear vacuoles, indicating hypercontracted atrophic fibers

skeletal muscle fibrosis ( J:187799 )

♀ • soleus muscles show more endomysial and perimysial fibrosis compared to muscle from single Dmd mutants

♀ • diaphragms show more fibrosis than single Dmd mutants

skeletal muscle endomysial fibrosis ( J:187799 )

♀ • in soleus muscles

impaired skeletal muscle regeneration ( J:187799 )

♀ • tibialis anterior muscle shows fewer central nuclei relative to muscle from single Dmd mutants, indicating reduction in repair of muscle damage

progressive muscle weakness ( J:187799 )

♀ • mutants become progressively weak

skeleton

kyphosis ( J:187799 )

♀ • mutants develop spine deformation resembling kyphosis by 6 months of age

♀ • spine deformation appears earlier and is more severe than in single Barx2 mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:187799

Genotype
MGI:6507848

cx15

• Allelic Composition: Dmd^mdx/Y; Tg(DMD*)#Spc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/10ScSn * DBA/2

muscle

myositis ( J:280218 )

♂ • muscle inflammation

skeletal muscle fibrosis ( J:280218 )

♂ • muscle shows features of fibrosis

dystrophic muscle ( J:280218 )

♂

immune system

myositis ( J:280218 )

♂ • muscle inflammation

homeostasis/metabolism

abnormal calcium level ( J:280218 )

♂ • muscle shows calcium deposits

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:280218

Genotype
MGI:3716189

cx16

• Allelic Composition: Dmd^mdx/?; Fgf2^tm1Zllr/Fgf2^tm1Zllr; Fgf6^tm1Thbr/Fgf6^tm1Thbr
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/10ScSn

muscle

muscle phenotype ( J:85088 )

N • growth and differentiation kinetics of myogenic cells are comparable to wild-type

abnormal skeletal muscle morphology ( J:85088 )

• pale areas in muscle contain extensive connective tissue

abnormal skeletal muscle fiber morphology ( J:85088 )

• when mice are injected with the diazo dye EBD, dye is taken up by damaged muscle fibers to varying degrees, but preferentially into the hindlimb; uptake occurs because of focal breakdown of plasmalemma which is an early event in necrosis

• some muscles are stained entirely indicating massive damage to the muscle fibers of the diaphragm and gluteus maximus whereas muscles in wild-type mice do not take up dye

increased variability of skeletal muscle fiber size ( J:85088 )

• in pale areas of muscles, remaining myotubes show large variation in caliber size

skeletal muscle fiber necrosis ( J:85088 )

• numerous necrotic fibers are present

decreased satellite cell number ( J:85088 )

• myotubes have slightly reduced percentage of satellite cells with respect to myotube nuclei in wild-type (3.05% vs 3.56%)

dystrophic muscle ( J:85088 )

• severe abnormalities are observed

abnormal muscle physiology ( J:85088 )

• mutants display palpable stiffness of the musculature, most evident in pelvic and shoulder girdle, at up to 6 months of age

skeleton

abnormal spine curvature ( J:85088 )

• up to 6 months of age, mice do not show clinical signs of severe dystrophy except for dorsal-ventral curvature of the spine

Genotype
MGI:2176891

cx17

• Allelic Composition: Dmd^mdx/Y; Dtna^tm1Jrs/Dtna^tm1Jrs; Utrn^tm1Jrs/Utrn^tm1Jrs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

mortality/aging

premature death ( J:59675 )

♂ • lifespan is 3-11 weeks

postnatal lethality, incomplete penetrance ( J:59675 )

♂ • 3 of 11 die before weaning

growth/size/body

postnatal growth retardation ( J:59675 )

♂ • exhibit poor growth

muscle

cardiomyopathy ( J:59675 )

♂ • develop a moderate to severe cardiomyopathy similar to that of double mutant Utrn^tm1Jrs and Dmd^mdx mice

skeletal muscle necrosis ( J:59675 )

♂

dystrophic muscle ( J:59675 )

♂ • develop severe skeletal dystrophy, however muscles are no more dystrophic than muscles of double Utrn^tm1Jrs and Dmd^mdx mutant mice

cardiovascular system

cardiomyopathy ( J:59675 )

♂ • develop a moderate to severe cardiomyopathy similar to that of double mutant Utrn^tm1Jrs and Dmd^mdx mice

skeleton

kyphosis ( J:59675 )

♂

limbs/digits/tail

abnormal limb morphology ( J:59675 )

♂ • severe limb contractures

nervous system

abnormal neuromuscular synapse morphology ( J:60776 )

♂ • distribution of acetylcholine receptors within synapse branches is abnormal, with a patchy or granular distribution

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:59675

Genotype
MGI:5795669

cx18

• Allelic Composition: Dmd^mdx/Y; Utrn^tm1Jrs/Utrn⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

immune system

diaphragmitis ( J:140282 )

♂ • endomysial inflammation in the diaphragm is more severe at 3 months of age than in single Dmd^mdx hemizygous males

myositis ( J:140282 )

♂ • endomysial inflammation in quadriceps is more severe at 3 months of age than in single Dmd^mdx hemizygous males

muscle

diaphragmitis ( J:140282 )

♂ • endomysial inflammation in the diaphragm is more severe at 3 months of age than in single Dmd^mdx hemizygous males

myositis ( J:140282 )

♂ • endomysial inflammation in quadriceps is more severe at 3 months of age than in single Dmd^mdx hemizygous males

skeletal muscle endomysial fibrosis ( J:140282 )

♂ • mice develop mild endomysial fibrosis in quadriceps at 6 months

♂ • endomysial fibrosis in the diaphragm is more severe than in single Dmd^mdx hemizygous males

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:140282

Genotype
MGI:2176876

cx19

• Allelic Composition: Dmd^mdx/Dmd^mdx; Utrn^tm1Jrs/Utrn^tm1Jrs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

mortality/aging

premature death ( J:42389 , J:59675 )

♀ • die between 4 and 14 weeks of age, with only half surviving beyond 8 weeks (J:42389)

♀ • lifespan is 4-20 weeks (J:59675)

growth/size/body

decreased body size ( J:42389 )

♀ • significantly smaller by 4 weeks of age

postnatal growth retardation ( J:42389 , J:59675 )

♀ • grow more slowly after 3 weeks of age (J:42389)

♀ (J:59675)

muscle

myocardium necrosis ( J:42389 )

♀ • large areas of necrotic myocytes with infiltrating mononuclear cells are present in 5 of 9 mutant hearts examined at 8 to 11 weeks of age

♀ • necrosis is most prominent in the epicardial surface of the right ventricle, but is seen throughout both ventricles, however ventricles are not dilated or hypertrophic

skeletal muscle interstitial fibrosis ( J:42389 )

♀ • seen by 10 weeks of age

skeletal muscle necrosis ( J:42389 )

♀ • necrosis begins earlier and persists longer than in single Dmd mutants and leads to fibrosis

dystrophic muscle ( J:42389 , J:59675 )

♀ • begin to exhibit symptoms of skeletal muscle disease at 4 weeks of age and severity progresses with age (J:42389)

♀ • develop severe skeletal muscle dystrophy (J:59675)

muscle degeneration ( J:42389 )

♀ • muscle degeneration begins earlier than in single Dmd mutants

abnormal muscle physiology ( J:42389 )

♀

cardiomyopathy ( J:42389 , J:59675 )

♀ (J:42389)

♀ • develop moderate to severe cardiomyopathy (J:59675)

abnormal muscle relaxation ( J:42389 )

♀ • relaxation time of muscle (time from peak force to baseline) is greatly prolonged

muscle weakness ( J:42389 )

♀ • sternomastoid muscle generates only 40-60% as much tension as controls in response to stimulation of its nerve, indicating weakness

cardiovascular system

myocardium necrosis ( J:42389 )

♀ • large areas of necrotic myocytes with infiltrating mononuclear cells are present in 5 of 9 mutant hearts examined at 8 to 11 weeks of age

♀ • necrosis is most prominent in the epicardial surface of the right ventricle, but is seen throughout both ventricles, however ventricles are not dilated or hypertrophic

cardiomyopathy ( J:42389 , J:59675 )

♀ (J:42389)

♀ • develop moderate to severe cardiomyopathy (J:59675)

nervous system

abnormal neuromuscular synapse morphology ( J:42389 , J:60776 )

♀ • exhibit fewer junctional folds in the neuromuscular junction (J:42389)

♀ • distribution of acetylcholine receptors within the synapse branches is abnormal, with a patchy distribution (J:60776)

limbs/digits/tail

abnormal limb morphology ( J:42389 , J:59675 )

♀ • exhibit contracted and stiff limbs at 4 weeks of age (J:42389)

♀ • severe limb contractures (J:59675)

skeleton

kyphosis ( J:42389 , J:59675 )

♀ (J:42389)

♀ (J:59675)

behavior/neurological

abnormal gait ( J:42389 )

♀ • abnormal waddling gait is seen at 4 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:42389 , J:59675

Genotype
MGI:3716196

cx20

• Allelic Composition: Dmd^mdx/?; Fgf2^tm1Zllr/Fgf2^tm1Zllr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn

muscle

dystrophic muscle ( J:85088 )

• mutants show dystrophic changes to the muscle fibers, although less severely than Fgf2/Fgf6/Dmd triple mutants

• changes are not enhanced compared to Dmd mutants

Genotype
MGI:2176879

cx21

• Allelic Composition: Dmd^mdx/Dmd^mdx; Utrn^tm1Ked/Utrn^tm1Ked
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn * DBA

mortality/aging

premature death ( J:42388 )

♀ • all succumb to premature death by 20 weeks of age

behavior/neurological

abnormal posture ( J:42388 )

♀ • slack posture by 4 to 6 weeks of age

abnormal gait ( J:42388 )

♀ • waddling gait

decreased locomotor activity ( J:42388 )

♀ • decrease in mobility and abnormal field behavior by 4 to 6 weeks of age

growth/size/body

weight loss ( J:42388 )

♀

muscle

abnormal skeletal muscle fiber morphology ( J:42388 )

♀ • muscle fibers are irregularly shaped and sized, many with centralized nuclei and some lymphocyte infiltration

♀ • some fibers contain fat or appear to be replaced by adipose cells

abnormal skeletal muscle fiber size ( J:42388 )

♀

centrally nucleated skeletal muscle fibers ( J:42388 )

♀

skeletal muscle interstitial fibrosis ( J:42388 )

♀

skeletal muscle necrosis ( J:42388 )

♀

dystrophic muscle ( J:42388 )

♀ • muscular dystrophy begins at 6 days of age and becomes severe by 10 weeks of age, earlier than in single Dmd mutants

progressive muscle weakness ( J:42388 )

♀

respiratory system

abnormal breathing pattern ( J:42388 )

♀ • exhibit abnormal breathing by 4 to 6 weeks of age

skeleton

kyphosis ( J:42388 )

♀

nervous system

abnormal neuromuscular synapse morphology ( J:42388 )

♀ • postsynaptic endplate regions exhibit a virtual absence of junctional folding at the postsynaptic membrane

♀ • about 40% decrease in acetylcholine receptors at the synapse

limbs/digits/tail

abnormal hindlimb morphology ( J:42388 )

♀ • abnormally postured hindlimbs with joint contractures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:42388

Genotype
MGI:5779560

cx22

• Allelic Composition: Ctss^tm1Hap/Ctss^tm1Hap; Dmd^mdx/Dmd^mdx
• Genetic Background: involves: 129S2/SvPas * C57BL/10ScSn

behavior/neurological

impaired exercise endurance ( J:230788 )

• treadmill running time is decreased as compared to wild-type, but increased as compared to homozygous Dmd^mdx mice

homeostasis/metabolism

impaired exercise endurance ( J:230788 )

• treadmill running time is decreased as compared to wild-type, but increased as compared to homozygous Dmd^mdx mice

increased circulating creatine kinase level ( J:230788 )

• increase in serum creatine kinase levels as compared to wild-type, but decreased as compared to homozygous Dmd^mdx mic

muscle

abnormal skeletal muscle fiber morphology ( J:230788 )

• decreased membrane stability as compared to wild-type, but increased as compared to homozygous Dmd^mdx mice

centrally nucleated skeletal muscle fibers ( J:230788 )

• increase in central nucleation at 2 and 10 months of age as compared to wild-type, but decreased as compared to homozygous Dmd^mdx mice

skeletal muscle fiber necrosis ( J:230788 )

• myofiber necrosis is increased as compared to wild-type, but decreased as compared to homozygous Dmd^mdx mic

skeletal muscle fibrosis ( J:230788 )

• fibrosis at 2 months and 10 months is increased as compared to wild-type, but decreased as compared to homozygous Dmd^mdx mice

dystrophic muscle ( J:230788 )

• increased as compared to wild-type, but decreased as compared to homozygous Dmd^mdx mice

Genotype
MGI:4940318

cx23

• Allelic Composition: Dmd^mdx/Dmd^mdx; Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/10ScSn

muscle

myositis ( J:162340 )

♀ • mice exhibit enhanced inflammatory response in skeletal muscles compared with Dmd^mdx homozygotes

decreased skeletal muscle fiber size ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

decreased skeletal muscle fiber diameter ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

skeletal muscle fiber degeneration ( J:162340 )

♀ • increased compared to in Dmd^mdx homozygotes

decreased skeletal muscle weight ( J:162340 )

♀ • in the tibialis anterior and gastrocnemius compared with Dmd^mdx homozygotes

dystrophic muscle ( J:162340 )

♀ • mice exhibit an exacerbated dystrophic phenotype compared with Dmd^mdx homozygotes

immune system

myositis ( J:162340 )

♀ • mice exhibit enhanced inflammatory response in skeletal muscles compared with Dmd^mdx homozygotes

behavior/neurological

decreased grip strength ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

growth/size/body

decreased body size ( J:162340 )

♀ • at 8 weeks compared with Dmd^mdx homozygotes

decreased body weight ( J:162340 )

♀ • at 8 weeks compared with Dmd^mdx homozygotes

Genotype
MGI:6114163

cx24

• Allelic Composition: Cav3^tm1Ncnp/Cav3⁺; Dmd^mdx/Dmd^mdx
• Genetic Background: involves: 129S4/SvJae * C57BL/10 * C57BL/10ScSn

muscle

abnormal muscle development ( J:150127 )

♀ • loss of hind limb Pax7+ myoblasts at E17.5

abnormal muscle fiber morphology ( J:150127 )

♀ • myotubes are hypotrophic in E13.5-E17.5 muscles

♀ • total myotube number per muscle is reduced

♀ • high number of centrally located myonuclei at E17.5

♀ • misalignment of myotubules in muscle at E13.5-E17.5

centrally nucleated skeletal muscle fibers ( J:150127 )

♀ • high number of centrally located myonuclei at E17.5

abnormal intercostal muscle morphology ( J:150127 )

♀ • extensive loss of intercostal muscle fibers at E17.5 with reduced intercostal muscle fiber density

♀ • 71.2% depletion of intercostal myotubes by E17.5

Genotype
MGI:3655093

cx25

• Allelic Composition: Dmd^mdx/Dmd⁺; Foxk1^tm1Djg/Foxk1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

growth/size/body

decreased body size ( J:62225 )

♀ • mice survive to adulthood but remain small in size

muscle

skeletal muscle necrosis ( J:62225 )

♀ • extensive muscle necrosis is observed up to 6 months of age

Genotype
MGI:4366782

cx26

• Allelic Composition: Dmd^mdx/Dmd⁺; Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♀ • mice show isolated dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♀ • moderate elevation of pyruvate kinase levels is detectable by P21, absence of Nos1 expression does not significantly change pyruvate kinase levels compared to mice heterozygous for both Dmd^mdx and Nos1^tm1Plh

Genotype
MGI:3655090

cx27

• Allelic Composition: Dmd^mdx/Y; Foxk1^tm1Djg/Foxk1^tm1Djg
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

mortality/aging

premature death ( J:62225 )

♂ • all are dead by 3 months of age

postnatal lethality, incomplete penetrance ( J:62225 )

♂ • die within a few weeks of birth

♂ • few survive beyond weaning

behavior/neurological

weakness ( J:62225 )

♂ • fragile and weak

decreased locomotor activity ( J:62225 )

♂

muscle

skeletal muscle fibrosis ( J:62225 )

♂ • fibrosis in muscles of the chest wall, the diaphragm and the intercostals

skeletal muscle necrosis ( J:62225 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:62225

Genotype
MGI:4366781

cx28

• Allelic Composition: Dmd^mdx/Y; Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♂ • mice show severe dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♂ • marked elevation of pyruvate kinase levels is detectable by P21, absence of Nos1 expression does not significantly change pyruvate kinase levels compared to mice hemizygous for Dmd^mdx and heterozygous for Nos1^tm1Plh

Genotype
MGI:3784305

cx29

• Allelic Composition: Dmd^mdx/?; Myod1^tm1Jae/Myod1^tm1Jae
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

Dmd^mdx/? Myod1^tm1Jae/Myod1^tm1Jae mice develop cardiomyopathy

mortality/aging

premature death ( J:52248 )

• premature death around 12 months of age

cardiovascular system

increased myocardial fiber size ( J:52248 )

• ventricles contain regions in which individual cardiac myocytes are enlarged; these hypertrophic myocytes are more common in the left ventricle than the right ventricle

• cardiac myocyte hypertrophy precedes necrosis

myocardium necrosis ( J:52248 )

• fibrotic areas are composed of necrotic myocytes

increased heart weight ( J:52248 )

abnormal heart ventricle morphology ( J:52248 )

• hearts show an increase in ventricular diameter without a change in the thickness of the ventricular wall

cardiac fibrosis ( J:52248 )

• more than 50% of mutants show evidence of fibrosis at 10 months of age, while more than 80% display extensive fibrosis by 12 months of age

• fibrosis is seen in the left ventricle and only rarely in the right ventricle and are confined primarily to the epicardial region of the left ventricle

cardiac interstitial fibrosis ( J:52248 )

• fibrotic areas are composed of necrotic myocytes associated with interstitial fibrosis

dilated cardiomyopathy ( J:52248 )

• progressive development of dilated cardiomyopathy that is evident by 5 months of age

muscle

increased myocardial fiber size ( J:52248 )

• ventricles contain regions in which individual cardiac myocytes are enlarged; these hypertrophic myocytes are more common in the left ventricle than the right ventricle

• cardiac myocyte hypertrophy precedes necrosis

myocardium necrosis ( J:52248 )

• fibrotic areas are composed of necrotic myocytes

dilated cardiomyopathy ( J:52248 )

• progressive development of dilated cardiomyopathy that is evident by 5 months of age

growth/size/body

increased heart weight ( J:52248 )

cellular

cardiac interstitial fibrosis ( J:52248 )

• fibrotic areas are composed of necrotic myocytes associated with interstitial fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:52248

Genotype
MGI:3655088

cx30

• Allelic Composition: Dmd^mdx/Dmd^mdx; Foxk1^tm1Djg/Foxk1^tm1Djg
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

mortality/aging

premature death ( J:62225 )

♀ • all are dead by 3 months of age

postnatal lethality, incomplete penetrance ( J:62225 )

♀ • die within a few weeks of birth

♀ • few survive beyond weaning

behavior/neurological

weakness ( J:62225 )

♀ • fragile and weak

decreased locomotor activity ( J:62225 )

♀

muscle

skeletal muscle fibrosis ( J:62225 )

♀ • fibrosis in muscles of the chest wall, the diaphragm and the intercostals

skeletal muscle necrosis ( J:62225 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:62225

Genotype
MGI:5438998

cx31

• Allelic Composition: Dag1^tm1.1Swin/Dag1^tm1.1Swin; Dmd^mdx/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn

homeostasis/metabolism

increased circulating creatine kinase level ( J:187750 )

♂ • less so than in Dmd^mdx homozygotes or hemizygotes

increased susceptibility to injury ( J:187750 )

♂ • muscles exhibit partial protection against contraction-induced injury compared with Dmd^mdx homozygotes or hemizygotes

muscle

centrally nucleated skeletal muscle fibers ( J:187750 )

♂ • less so than in Dmd^mdx homozygotes or hemizygotes

Genotype
MGI:3716195

cx32

• Allelic Composition: Dmd^mdx/?; Fgf6^tm1Thbr/Fgf6^tm1Thbr
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn

skeleton

abnormal spine curvature ( J:42574 )

• dorso-ventral curvature of the spine

muscle

muscle phenotype ( J:42574 )

N • no clinical signs of severe dystrophy for up to 6 months

abnormal epaxial muscle morphology ( J:42574 )

• back and body wall musculature show changes similar to diaphragm but less uniformly and more focally distributed

abnormal hypaxial muscle morphology ( J:42574 )

• muscle changes similar to diaphragm but less uniformly and more focally distributed

abnormal diaphragm morphology ( J:42574 )

• pronounced increase in collagen

• increase in mononuclear cells

• unusually small myotubes with very few centrally located nuclei

dystrophic muscle ( J:85088 )

• changes are not enhanced compared to Dmd mutants

myopathy ( J:42574 )

• severe myopathy observed in diaphragm, limb muscles, and back muscles

Genotype
MGI:5438997

cx33

• Allelic Composition: Dag1^tm1.1Swin/Dag1^tm1.1Swin; Dmd^mdx/Dmd^mdx
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/10ScSn

homeostasis/metabolism

increased circulating creatine kinase level ( J:187750 )

♀ • less so than in Dmd^mdx homozygotes or hemizygotes

increased susceptibility to injury ( J:187750 )

♀ • muscles exhibit partial protection against contraction-induced injury compared with Dmd^mdx homozygotes or hemizygotes

muscle

centrally nucleated skeletal muscle fibers ( J:187750 )

♀ • less so than in Dmd^mdx homozygotes or hemizygotes

Genotype
MGI:4361735

cx34

• Allelic Composition: Dmd^mdx/Dmd^mdx; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn

Reduced diaphragm and cardiac fibrosis in Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh and Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh mice compared to Dmd^mdx/Dmd^mdx mice

immune system

decreased granulocyte number ( J:150572 )

♀ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♀ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♀ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♀ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♀ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

muscle

abnormal muscle physiology ( J:150572 )

♀ • mice exhibit improved muscle regeneration and reduced muscle inflammation and fibrosis in the diaphragm and heart compared with Dmd^mdx homozygotes

behavior/neurological

abnormal physical strength ( J:150572 )

♀ • at 4 and 8 weeks, mice exhibit increased strength on a wire and grip test compared with Dmd^mdx homozygotes

hematopoietic system

decreased granulocyte number ( J:150572 )

♀ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♀ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♀ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♀ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♀ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

Genotype
MGI:4361734

cx35

• Allelic Composition: Dmd^mdx/Y; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn

Reduced diaphragm and cardiac fibrosis in Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh and Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh mice compared to Dmd^mdx/Dmd^mdx mice

immune system

decreased granulocyte number ( J:150572 )

♂ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♂ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♂ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♂ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♂ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

muscle

abnormal muscle physiology ( J:150572 )

♂ • mice exhibit improved muscle regeneration and reduced muscle inflammation and fibrosis in the diaphragm and heart compared with Dmd^mdx homozygotes

behavior/neurological

abnormal physical strength ( J:150572 )

♂ • at 4 and 8 weeks, mice exhibit increased strength on a wire and grip test compared with Dmd^mdx homozygotes

hematopoietic system

decreased granulocyte number ( J:150572 )

♂ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♂ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♂ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♂ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♂ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

Genotype
MGI:4936867

cx36

• Allelic Composition: Dmd^mdx/Y; Terc^tm1Rdp/Terc⁺
• Genetic Background: involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL

muscle

centrally nucleated skeletal muscle fibers ( J:167294 )

♂

abnormal diaphragm morphology ( J:167294 )

♂ • diaphragms exhibit increased diameter compared with control mice

abnormal muscle physiology ( J:167294 )

♂ • muscle stem cell proliferation in undamaged muscles is higher than in control mice

homeostasis/metabolism

increased circulating creatine kinase level ( J:167294 )

♂ • with increasing age

Genotype
MGI:4936865

cx37

• Allelic Composition: Dmd^mdx/Y; Terc^tm1Rdp/Terc^tm1Rdp
• Genetic Background: involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL

mortality/aging

premature death ( J:167294 )

♂ • second generation mice beginning at 48 weeks of age likely due to respiratory failure

muscle

abnormal skeletal muscle morphology ( J:167294 )

♂ • first and second generation mice exhibit a progressive reduction in revertant myofiber cluster size compared to in control mice

increased variability of skeletal muscle fiber size ( J:167294 )

♂ • at 8 weeks in second generation mice

centrally nucleated skeletal muscle fibers ( J:167294 )

♂ • in first and second generation mice

abnormal diaphragm morphology ( J:167294 )

♂ • diaphragms in first and second generation mice exhibit increased diameter compared with control mice

♂ • by 76 weeks, diaphragm muscle is atrophied unlike in control mice

decreased satellite cell number ( J:167294 )

♂ • in aged second generation mice

skeletal muscle degeneration ( J:167294 )

♂ • in second generation mice with age

skeletal muscle fibrosis ( J:167294 )

♂ • in second generation mice

skeletal muscle necrosis ( J:167294 )

♂ • at 8 weeks in second generation mice

calcified muscle ( J:167294 )

♂ • second generation mice exhibit calcium depositions in the muscles unlike control mice

dystrophic muscle ( J:167294 )

♂ • second generation mice exhibit progressive muscular dystrophy with age unlike control mice

♂ • however, dystrophic phenotypes are improved by transplantation with wild-type muscle stem cells

muscular atrophy ( J:167294 )

♂ • in first and second generation mice prior to and after damage

abnormal muscle physiology ( J:167294 )

♂ • at 8 weeks, second generation mice exhibit increased myofiber membrane permeability compared with control mice

♂ • second generation mice exhibit impaired muscle stem cell proliferation compared with control mice

♂ • muscle stem cells from second generation mice exhibit impaired proliferative potential in culture compared with control cells

♂ • muscle stem cells from second generation mice exhibit impaired engrafting after transplantation compared with control cells

myositis ( J:167294 )

♂ • at 8 weeks in second generation mice

abnormal muscle electrophysiology ( J:167294 )

♂ • at 8 weeks, first and second generation mice exhibit decreased muscle twitch force, tetanic force, and tetanic tension compared with control mice

muscle weakness ( J:167294 )

♂ • at 8 weeks, second generation mice spend less time running on a treadmill than control mice

♂ • at 8 weeks, second generation mice hold onto a grid for less time than control mice

homeostasis/metabolism

impaired exercise endurance ( J:167294 )

♂ • at 8 weeks, second generation mice spend less time running on a treadmill than control mice

increased circulating creatine kinase level ( J:167294 )

♂ • at 8 weeks in second generation mice, but declining after 60 weeks of age

cellular

decreased telomere length ( J:167294 )

♂ • myoblasts from first and second generation exhibit shortened telomeres compared with control cells

chromosomal instability ( J:167294 )

♂ • myoblasts from first and second generation exhibit fused chromosomes unlike control cells

skeleton

kyphosis ( J:167294 )

♂ • in aged second generation mice

respiratory system

respiratory failure ( J:167294 )

♂ • second generation mice beginning at 48 weeks of age likely due to respiratory failure

immune system

myositis ( J:167294 )

♂ • at 8 weeks in second generation mice

behavior/neurological

impaired exercise endurance ( J:167294 )

♂ • at 8 weeks, second generation mice spend less time running on a treadmill than control mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:167294

Genotype
MGI:2176892

cx38

• Allelic Composition: Dmd^mdx/Y; Dtna^tm1Jrs/Dtna^tm1Jrs
• Genetic Background: involves: 129X1/SvJ * C57BL/10ScSn

mortality/aging

premature death ( J:59675 )

♂ • life span is 8-10 months

muscle

cardiomyopathy ( J:59675 )

♂ • develop moderate to severe cardiomyopathy

dystrophic muscle ( J:59675 )

♂ • exhibit a more severe dystrophy than single Dmd^mdx mutant mice, but not as severe as that of double mutant Utrn^tm1Jrs and Dmd ^mdx mice or triple mutant Utrn^tm1Jrs, Dtna^tm1Jrs, and Dmd^mdx mice

cardiovascular system

cardiomyopathy ( J:59675 )

♂ • develop moderate to severe cardiomyopathy

nervous system

abnormal neuromuscular synapse morphology ( J:60776 )

♂ • at 2-4 months of age, synapses are broken into discrete boutons and acetylcholine receptors are patchily distributed within the boutons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:59675

Genotype
MGI:4889211

cx39

• Allelic Composition: Cmah^tm1Avrk/Cmah^tm1Avrk; Dmd^mdx/Dmd^mdx
• Genetic Background: involves: 129X1/SvJ * C57BL/10ScSn

mortality/aging

premature death ( J:164594 )

♀ • 50% of mice dying by 11 months of age

♀ • mice exhibit decreased life span compared with Dmd^mdx homozygotes

muscle

cardiac muscle necrosis ( J:164594 )

♀ • by 3 months, mice exhibit necrotic foci in the heart unlike wild-type mice

skeletal muscle fibrosis ( J:164594 )

♀ • in the quadriceps at 6 weeks of age

♀ • fibrosis in the diaphragm is increased compared to in Dmd^mdx homozygotes

dystrophic muscle ( J:164594 )

♀ • more severe than in Dmd^mdx homozygotes

muscle weakness ( J:164594 )

♀ • at 8 months, mice exhibit impaired diaphragm and cardiac peak force compared with Dmd^mdx homozygotes

behavior/neurological

impaired coordination ( J:164594 )

♀ • at 8 months on a rotarod to a greater extent than in Dmd^mdx homozygotes

abnormal gait ( J:164594 )

♀ • at 8 months to a greater extent than in Dmd^mdx homozygotes

immune system

increased macrophage cell number ( J:164594 )

♀ • in muscles compared to in Dmd^mdx homozygotes

increased monocyte cell number ( J:164594 )

♀ • in muscles compared to in Dmd^mdx homozygotes

hematopoietic system

increased macrophage cell number ( J:164594 )

♀ • in muscles compared to in Dmd^mdx homozygotes

increased monocyte cell number ( J:164594 )

♀ • in muscles compared to in Dmd^mdx homozygotes

cardiovascular system

cardiac muscle necrosis ( J:164594 )

♀ • by 3 months, mice exhibit necrotic foci in the heart unlike wild-type mice

Genotype
MGI:5490611

cx40

• Allelic Composition: Dmd^mdx/Dmd^mdx; Prkdc^scid/Prkdc^scid
• Genetic Background: involves: BALB/c * C57BL/10ScSn * C57BL/Ka

hematopoietic system

decreased B cell number ( J:125527 )

• 9.3% of total blood derived cells express B220+ and no expression of CD19+ cells as determined by cytofluorimetric analysis

absent CD4-positive, alpha-beta T cells ( J:125527 )

• no expression of CD4+ cells as determined by cytofluorimetric analysis

absent CD8-positive, alpha-beta T cells ( J:125527 )

• no expression of CD8+ cells as determined by cytofluorimetric analysis

homeostasis/metabolism

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• higher endurance on treadmill in double mutant than Dmd^mdx mutants

decreased transforming growth factor beta level ( J:125527 )

• costal diaphragm (DIA) has a lower quantity of active TGFB1 in comparison to Dmd^mdx mutant although total quantity is similar

• tibialis anterior (TA) and quadricepts (QA) muscles have a lower quantity of total TGFB1 in comparison to Dmd^mdx mutant

immune system

decreased B cell number ( J:125527 )

• 9.3% of total blood derived cells express B220+ and no expression of CD19+ cells as determined by cytofluorimetric analysis

absent CD4-positive, alpha-beta T cells ( J:125527 )

• no expression of CD4+ cells as determined by cytofluorimetric analysis

absent CD8-positive, alpha-beta T cells ( J:125527 )

• no expression of CD8+ cells as determined by cytofluorimetric analysis

muscle

increased skeletal muscle fiber diameter ( J:125527 )

• area of muscle fibers is 1500-1800 um² and coefficient of variance is 55-65

centrally nucleated skeletal muscle fibers ( J:125527 )

• small, centrally nucleated, regenerating muscle fibers are found in 2 and 12 month old mice

• 46-52% of muscle fibers exhibit centrally located nuclei

skeletal muscle fiber degeneration ( J:125527 )

• degenerating muscle fibers are found in 2 and 12 month old mice

skeletal muscle fibrosis ( J:125527 )

• aged 12 month old double mutant mice exhibit fibrosis, but less than in age-matched Dmd^mdx mice

impaired skeletal muscle contractility ( J:125527 )

• loss of normalized tetanic force in the costal diaphragm (DIA) strips is observed in 2 and 12 month old mice as compared to wild type

• change appears lower in double mutant than in Dmd^mdx mutants

• a similar decrease in normalized tetanic force occurs in the tibialis anterior (TA)

reproductive system

reduced fertility ( J:125527 )

• double mutant mice are less fertile than Dmd^mdx mice

skeleton

abnormal vertebral column morphology ( J:125527 )

• progressive spinal deformity

behavior/neurological

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• higher endurance on treadmill in double mutant than Dmd^mdx mutants

Genotype
MGI:5521335

cx41

• Allelic Composition: Dmd^mdx/Y; Foxn1^nu/Foxn1^nu
• Genetic Background: involves: C57BL/10ScSn

muscle

abnormal muscle morphology ( J:95776 )

♂ • elevated hydroxyproline levels in the heart, tibialis anterior and soleus when normalized to wet weight but not on a per muscle basis in mice at 3 weeks of age but not at 24 weeks of age

♂ • unlike in mice homozygous for Dmd^mdx alone, necrosis has not started at 3 weeks of age

decreased skeletal muscle fiber size ( J:95776 )

♂ • in the tibialis anterior at 3 weeks of age

increased skeletal muscle fiber size ( J:95776 )

♂ • in the soleus muscles at 3 weeks of age

Genotype
MGI:5903046

cx42

• Allelic Composition: Dmd^mdx/Y; Mirc37^tm1Boet/Mirc37^tm1Boet
• Genetic Background: involves: C57BL/10ScSn

muscle

dystrophic muscle ( J:241493 )

• as in Dmd^mdx homozygotes

homeostasis/metabolism

increased creatine kinase activity ( J:241493 )

• as in Dmd^mdx homozygotes

Genotype
MGI:5428739

cx43

• Allelic Composition: Dmd^mdx/Dmd^mdx; Tg(ACTA1-SSPN)3.0Rcros/0
• Genetic Background: involves: C57BL/10ScSn

muscle

abnormal sarcolemma morphology ( J:185346 )

♀ • dystrophic pathology observed in Dmd^mdx mice is ameliorated with a decrease in centrally localized nuclei in skeletal muscles and reduced sarcolemmal membrane damage

centrally nucleated skeletal muscle fibers ( J:185346 )

♀ • dystrophic pathology observed in Dmd^mdx mice is ameliorated with a decrease in centrally localized nuclei in skeletal muscles and reduced sarcolemmal membrane damage

dystrophic muscle ( J:185346 )

♀ • dystrophic pathology observed in Dmd^mdx mice is ameliorated with a decrease in centrally localized nuclei in skeletal muscles and reduced sarcolemmal membrane damage

Genotype
MGI:6258417

cx44

• Allelic Composition: Dmd^mdx/Dmd^mdx; Selenos^tm1.1Sfa/Selenos⁺
• Genetic Background: involves: C57BL/6 * C57BL/10ScSn

homeostasis/metabolism

increased carbon dioxide production ( J:266872 )

• compared with Dmd^mdx homozygotes during the first two active hours at night

increased oxygen consumption ( J:266872 )

• compared with Dmd^mdx homozygotes during the first two active hours at night

abnormal respiratory quotient ( J:266872 )

• elevated as in Dmd^mdx homozygotes relative to wild-type mice

growth/size/body

decreased body mass index ( J:266872 )

• between 6 and 12 weeks compared with Dmd^mdx homozygotes

decreased lean body mass ( J:266872 )

• between 6 and 12 weeks compared with Dmd^mdx homozygotes

muscle

muscle phenotype ( J:266872 )

N • extensor digitalis longus and soleus muscles wet weight is normal

abnormal skeletal muscle fiber type ratio ( J:266872 )

• increased number of small fibres and fewer large fibres than in Dmd^mdx homozygotes

• however, there was no difference in the number of central nuclei suggesting normal regeneration

Genotype
MGI:6478907

cx45

• Allelic Composition: Dmd^mdx/Dmd^mdx; Snhg15^tm1Nju/Snhg15^tm1Nju
• Genetic Background: involves: C57BL/6J * C57BL/10ScSn

growth/size/body

growth/size/body region phenotype ( J:291983 )

N • normal body size and weight

muscle

muscle phenotype ( J:291983 )

N • normal tibialis anterior (TA) and gastrocnemius (GAS) muscle weight at age 8 weeks

increased variability of skeletal muscle fiber size ( J:291983 )

• more small diameter muscle fibers in tibialis anterior (TA) muscle weight at age 8 weeks

skeletal muscle fibrosis ( J:291983 )

• increased diaphragm muscle fibrosis at age 6-8 months

impaired skeletal muscle regeneration ( J:291983 )

• increased size of unrepaired areas in tibialis anterior (TA) muscle weight at age 8 weeks

• increased number of embryonic myosin heavy chain expressing myofibers in tibialis anterior (TA) muscle weight at age 8 weeks

• increased CD68+ macrophage infiltration in tibialis anterior (TA) muscle weight at age 8 weeks

Genotype
MGI:3798607

ot46

• Allelic Composition: Dmd^mdx/Y
• Genetic Background: C57BL/10ScSn-Dmd^mdx

muscle

muscle phenotype ( J:177391 )

♂N • limb and diaphragm muscle weights are similar to controls in mice at 1 year of age

abnormal atrium myocardial trabeculae morphology ( J:150127 )

♂ • atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

abnormal myocardial fiber morphology ( J:150127 )

♂ • cardiac myocyte disorganization

myocardial fiber degeneration ( J:9638 )

♂ • unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

abnormal muscle development ( J:150127 )

♂ • cultured embryonic muscle stem cells from E11.5 to E17.5 exhibit hyperproliferation and apoptosis

♂ • Pax7+ skeletal muscle stem cell population is reduced and disorganized at E17.5

abnormal myotube morphology ( J:150127 )

♂ • myotube alignment is disrupted early in myogenesis

♂ • myotubes are hypotrophic in E13.5-E17.5 muscles

♂ • myotube width varies more in E13.5-E17.5 muscles than in wild-type muscle

♂ • myotube defects occur earlier in intercostals at E13.5 than proximal limb muscles at E15.5

♂ • misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

♂ • myonuclei are more frequently located centrally and slightly further apart in the myotube at E15.5

♂ • only central nuclei (not peripheral) are present in E15.5 muscles

♂ • muscles exhibit a small reduction in myotube number at E13.5-E17.5

abnormal skeletal muscle fiber morphology ( J:152525 )

♂ • at 15 days of age necrotic fibers are found, occassionally in clusters, at 20 days of age necrotic fibers are numerous as are groups of regenerating fibers with internally placed nuclei, necrotic fibers are most numerous between 30 and 60 days of age and gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but there is almost no fibrous tissue proliferation or adipose tissue replacement

centrally nucleated skeletal muscle fibers ( J:150127 , J:152525 )

♂ • only central nuclei (not peripheral) are present in E15.5 muscles (J:150127)

♂ (J:152525)

skeletal muscle fiber degeneration ( J:9638 )

♂ • mice exhibit skeletal muscle fiber degeneration with phagocytosis unlike in wild-type mice

skeletal muscle fiber necrosis ( J:152525 )

♂

abnormal intercostal muscle morphology ( J:150127 )

♂ • misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

♂ • intercostal muscle fibers are distributed more sparsely at E17.5 and fetuses have reduced intercostal muscle fiber densities

♂ • 37.5% depletion of intercostal myotubes by E17.5

skeletal muscle fibrosis ( J:177391 )

♂ • increased collagen deposition in the diaphragm and quadriceps muscles between 12 weeks and 1 year of age

abnormal muscle contractility ( J:152525 )

♂ • scattered hypercontracted fibers are found by electron microscopy at 10 days of age

impaired skeletal muscle contractility ( J:177391 )

♂ • decrease in the tetanic force produced by the diaphragm and extensor digitorum longus muscles compared to wild-type controls

impaired muscle relaxation ( J:9638 )

♂ • electromyograms reveal peudomyotonia unlike in wild-type mice

behavior/neurological

behavior/neurological phenotype ( J:177391 )

♂N • performance in a rotarod assay is not significantly different from controls in mice at 6 - 20 weeks of age

decreased grip strength ( J:177391 )

♂ • in fore and hind paws

abnormal gait ( J:177391 )

♂ • increased hind paw base width

short stride length ( J:177391 )

♂ • at 1 year of age

fatigue ( J:177391 )

♂ • at 6 weeks of age, display a decrease in rearings after exercise compared to wild-type controls

♂ • at 12 weeks of age, display a decrease in ambulation and increase in rest time after exercise compared to wild-type controls

♂ • at 1 year of age, display a decrease in distance traveled after exercise compared to wild-type controls

♂ • interindividual responses to exercise induced fatigue are highly variable

adipose tissue

decreased body fat mass ( J:177391 )

♂ • decrease in the accumulation of abdominal fat compared to wild-type controls

growth/size/body

decreased body fat mass ( J:177391 )

♂ • decrease in the accumulation of abdominal fat compared to wild-type controls

decreased body weight ( J:177391 )

♂ • between 8 and 20 weeks of age compared to wild-type controls

♂ • however, body size as determined by measures of tibia length or body length is similar to wild-type controls

cardiovascular system

abnormal myocardial fiber morphology ( J:150127 )

♂ • cardiac myocyte disorganization

myocardial fiber degeneration ( J:9638 )

♂ • unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

abnormal heart atrium morphology ( J:150127 )

♂ • distention or separation of the myocardial and endocardial cell layers of the atria occurs at E17.5

abnormal atrium myocardial trabeculae morphology ( J:150127 )

♂ • atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

thick ventricular wall ( J:150127 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:150127 , J:177391

Genotype
MGI:3789123

ot47

• Allelic Composition: Dmd^mdx/Y
• Genetic Background: C57BL/10ScSn-Dmd^mdx/J

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:7361 )

♂

tremors ( J:7361 )

♂ • muscular tremors noticeable by 12 months of age

impaired coordination ( J:7361 )

♂ • mild incoordination noticeable by 12 months of age

immune system

increased interferon-gamma secretion ( J:150572 )

♂ • in splenocytes at 2 weeks of age

increased interleukin-12 secretion ( J:150572 )

♂ • in splenocytes at 2 weeks of age

increased interleukin-2 secretion ( J:150572 )

♂ • in splenocytes at 2 weeks and 2 years of age

increased interleukin-4 secretion ( J:150572 )

♂ • in splenocytes at 2 weeks, 4 weeks, and 2 years of age

increased interleukin-6 secretion ( J:150572 )

♂ • in splenocytes at 2 weeks of age

increased tumor necrosis factor secretion ( J:150572 )

♂ • in splenocytes at 2 weeks of age

homeostasis/metabolism

increased circulating creatine kinase level ( J:7361 )

♂ • exhibit elevated blood levels of creatine kinase

abnormal circulating pyruvate kinase level ( J:7361 )

♂ • exhibit elevated blood levels of pyruvate kinase

muscle

abnormal muscle morphology ( J:7361 )

♂

dilated sarcoplasmic reticulum ( J:7361 )

♂

abnormal skeletal muscle fiber morphology ( J:7361 )

♂ • development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina

♂ • the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

increased variability of skeletal muscle fiber size ( J:7361 )

♂ • variable muscle fiber size; progressive starting at 3 weeks of age

skeletal muscle fibrosis ( J:7361 )

♂ • exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis ( J:7361 )

♂ • progressive starting at 9 weeks of age

dystrophic muscle ( J:7361 )

♂

muscle degeneration ( J:7361 )

♂ • progressive starting at 3 weeks of age

muscular atrophy ( J:7361 )

♂ • progressive starting at 3 weeks of age

abnormal muscle physiology ( J:3666 )

♂ • increased intracellular sodium concentration in muscle; increased severity with age

myopathy ( J:7361 )

♂ • progressive degenerative myopathy; increased severity with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:7361

Genotype
MGI:4366784

ot48

• Allelic Composition: Dmd^mdx/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♂ • mice show severe dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♂ • marked elevation of pyruvate kinase levels is detectable by P21

Genotype
MGI:4359635

ot49

• Allelic Composition: Dmd^mdx/Y
• Genetic Background: involves: C57BL/10ScSn

immune system

diaphragmitis ( J:140282 )

♂ • at 3 months of age, the diaphragm shows multiple endomysial foci of mononuclear inflammatory cells

myositis ( J:140282 )

♂ • at 3 months of age, quadriceps show multiple endomysial foci of mononuclear inflammatory cells

♂ • however, at 6 months, endomysial inflammation is reduced in quadriceps and only scattered inflammatory cells are present

muscle

diaphragmitis ( J:140282 )

♂ • at 3 months of age, the diaphragm shows multiple endomysial foci of mononuclear inflammatory cells

myositis ( J:140282 )

♂ • at 3 months of age, quadriceps show multiple endomysial foci of mononuclear inflammatory cells

♂ • however, at 6 months, endomysial inflammation is reduced in quadriceps and only scattered inflammatory cells are present

abnormal skeletal muscle fiber morphology ( J:152749 )

♂ • the extensor digitorum longus, but not the soleus, at 32 weeks of age has a greater proportion of fast-twitch-oxidative-glycolytic fibers and a smaller proportion of fast-twitch-glycolytic fibers than controls

increased skeletal muscle fiber diameter ( J:19034 , J:152749 )

♂ • although the number of fibers is normal, the cross-sectional area of the fibers of the tibialis anterior is larger than normal at 3 and 6 months of age (J:19034)

♂ • at 32 weeks of age in the soleus fast-twitch-oxidative-glycolytic fibers have a larger cross-sectional area than those of controls (J:152749)

♂ • at 32 weeks of age in the extensor digitorum longus muscle both the slow-twitch-oxidative and fast-twitch-glycolytic fibers have a larger cross-sectional area than those of controls (J:152749)

centrally nucleated skeletal muscle fibers ( J:19034 )

♂ • peripherally nucleated fibers replace the normal fibers in the tibialis anterior, extensor digitorum longus, plantaris, and soleus in a progressive manner, reaching a plateau of 80-90% of fibers at 26 weeks of age

abnormal diaphragm morphology ( J:95776 , J:152891 )

♂ • elevated hydroxyproline in the diaphragm at 24 weeks of age but not at 3 weeks of age (J:95776)

♂ • unlike skeletal muscle, the diaphragm undergoes progressive degeneration without regeneration such that, although at 30 days of age foci of myofiber degeneration, necrosis, mineralization, and regeneration are present but not extensive, at 6 months of age the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibers are ensheathed in dense collagenous tissue with most having architectural aberrations (J:152891)

♂ • at 16 months of age there are twice normal levels of slow myosin in the diaphragm, a decrease in isometric force generation, and a shortened fiber length (J:152891)

♂ • at 1.5 years of age the diaphragm is found to have significantly reduced passive stretch capacity although overt respiratory compromise is not found in aging mutants (J:152891)

abnormal intercostal muscle morphology ( J:152891 )

♂ • the anterior scalene and intercostal muscles at 1 to 1.5 years of age have dystrophic changes similar to those of the diaphragm at 6 months of age

increased skeletal muscle mass ( J:19034 )

♂ • the cross-sectional area and wet weight of the tibialis anterior is greater than normal by 10 weeks of age

skeletal muscle hypertrophy ( J:19034 )

♂ • detectable up to 12 months of age but not at 15 months of age, at which point muscle fibers appear atrophied and extensively split

skeletal muscle endomysial fibrosis ( J:19034 , J:140282 )

♂ • found with age in the soleus and plantaris (J:19034)

♂ • mice develop progressive endomysial fibrosis with increased collagen III deposition in the diaphragm (J:140282)

skeletal muscle necrosis ( J:95776 )

♂ • conspicuous necrosis and regeneration at 3 weeks of age

skeletal muscle fiber necrosis ( J:19034 )

♂ • scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on

abnormal muscle electrophysiology ( J:142492 )

♂ • at 23 degrees hemidiaphragm preparations show lower than normal resting membrane potentials and insertion of a glass microelectrode into a single muscle fiber results in repetitive bursts of muscle action potentials in 30 to 50% of fibers, while at 37 degrees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal

abnormal muscle tone ( J:152749 )

♂ • at 4 weeks of age the soleus muscle has decreased twitch and tetanus tension compared with controls, but this is normal by 32 weeks of age

♂ • at 3 and 32 weeks of age the extensor digitorum longus muscle has decreased twitch and tetanus tension and faster time-to-peak twitch tension compared with controls and the maximum velocity of unloaded shortening is also decreased at 32 weeks of age

vision/eye

vision/eye phenotype ( J:23375 )

♂N • hemizygous males between 20 and 24 weeks of age have normal ERG readings even though abnormal b-waves are often found in Duchenne Muscular Dystrophy patients and are found in the mdx-3cv hemizygotes

nuclear cataract ( J:142492 )

♂ • nuclear opacity of the lens is found at 1 day of age

anterior subcapsular cataract ( J:142492 )

♂ • a slight anterior subcapsular opacity is seen at 4 days of age, which spreads anteriorly such that at 150 days of age there is complete anterior subcapsular opacity in addition to the nuclear opacity

nervous system

nervous system phenotype ( J:121319 )

♂N • at 8 weeks of age miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents, and the number of acetylcholine receptors at the postsynaptic membrane are all normal

abnormal neuromuscular synapse morphology ( J:121319 )

♂ • although the nerve terminal innervation of epitronchleoanoconeus muscle is normal, the terminal architecture of regenerated muscle fibers, those with central nuclei, are more complex than normal with an increase in the number of fine terminal arborizations, many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcholinesterase staining in close association

♂ • electron microscopy shows that neuromuscular junction postsynaptic membranes are variably simplified with a reduction in the number of secondary synaptic folds

Genotype
MGI:3716194

ot50

• Allelic Composition: Dmd^mdx/?
• Genetic Background: B6.B10ScSn-Dmd^mdx

muscle

abnormal skeletal muscle morphology ( J:85088 )

• muscles contain occasional patches of pale tissue which are primarily connective tissue

abnormal skeletal muscle fiber morphology ( J:85088 )

• when mice are injected with the diazo dye EBD, dye is taken up by damaged muscle fibers to varying degrees, but preferentially into the hindlimb; uptake occurs because of focal breakdown of plasmalemma which is an early event in necrosis

• muscles are not stained homogeneously, but streaks of dye representing damaged muscle fibers are observed in the muscle fibers of the diaphragm and gluteus maximus; damage is less severe than in Fgf2/Fgf6/Dmd triple mutants

dystrophic muscle ( J:85088 )

• mutants show dystrophic changes to the muscle fibers, although less severely than Fgf2/Fgf6/Dmd triple mutants