Phenotypes associated with this allele

• Allele Symbol: Tg(ACTA1-cre)79Jme
• Allele Name: transgene insertion 79, Judith Melki
• Allele ID: MGI:2447635
• Summary: 24 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ncor1^tm1.1Ics/Ncor1^tm1.1Ics Tg(ACTA1-cre)79Jme/0	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:5305236
cn2	Cox15^tm1.1Zev/Cox15^tm1.1Zev Tg(ACTA1-cre)79Jme/0	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:5292122
cn3	Hspb7^tm1.1Yty/Hspb7^tm1.1Yty Tg(ACTA1-cre)79Jme/0	involves: 129 * C57BL/6J * SJL	MGI:6118901
cn4	Smn1^tm1Jme/Smn1^tm1.1Jme Tg(ACTA1-cre)79Jme/0	involves: 129 * C57BL/6J * SJL	MGI:3721894
cn5	Actg1^tm1Erv/Actg1^tm1Erv Tg(ACTA1-cre)79Jme/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3688083
cn6	Actg1^tm1.2Erv/Actg1^tm1.2Erv Tg(ACTA1-cre)79Jme/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4881929
cn7	Pik3r4^tm1.1Mpnd/Pik3r4^tm1.1Mpnd Tg(ACTA1-cre)79Jme/0	involves: 129S2/SvPas * C57BL/6J * C57BL/6N * SJL	MGI:5499166
cn8	Csnk2b^tm1.1Bb/Csnk2b^tm1.1Bb Tg(ACTA1-cre)79Jme/?	involves: 129S2/SvPasCrl * C57BL/6J * SJL	MGI:3720797
cn9	Mtor^tm1.2Koz/Mtor^tm1.2Koz Tg(ACTA1-cre)79Jme/?	involves: 129S4/SvJae * C57BL/6J * SJL	MGI:4849944
cn10	Gabpa^tm1Sjb/Gabpa^tm1.1Sjb Tg(ACTA1-cre)79Jme/0	involves: 129S6/SvEvTac * C57BL/6	MGI:3714846
cn11	Gt(ROSA)26Sor^tm1(DUX4)Sqh/Gt(ROSA)26Sor^+ Tg(ACTA1-cre)79Jme/0	involves: 129S6/SvEvTac * C57BL/6J * SJL	MGI:6280330
cn12	Rxfp2^tm1Aia/Rxfp2^tm1c(EUCOMM)Wtsi Tg(ACTA1-cre)79Jme/0	involves: 129S7/SvEvBrd * C57BL/6J * C57BL/6N * SJL	MGI:5473317
cn13	Lrp4^tm1.1Line/Lrp4^tm1.1Line Mnx1^tm4(cre)Tmj/Mnx1^+ Tg(ACTA1-cre)79Jme/0	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * C57BL/6J * SJL	MGI:5440761
cn14	Lrp4^tm1.1Line/Lrp4^tm1.1Line Tg(ACTA1-cre)79Jme/0	involves: 129S/SvEv * C57BL/6 * C57BL/6J * SJL	MGI:5440759
cn15	Mtm1^tm1.2Jman/Y Tg(ACTA1-cre)79Jme/?	involves: 129T1/Sv * C57BL/6 * SJL	MGI:3720805
cn16	Gabpa^tm1Pjh/Gabpa^tm1Pjh Tg(ACTA1-cre)79Jme/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:3712148
cn17	Ar^tm2Ska/Ar^tm2Ska Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj * SJL	MGI:7647260
cn18	Acad9^tm1c(KOMP)Wtsi/Acad9^tm1c(KOMP)Wtsi Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * C57BL/6N * FVB/N * SJL	MGI:7378413
cn19	Cfl2^tm1Itl/Cfl2^tm1Itl Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * C57BL/6NTac * SJL	MGI:5316090
cn20	Sod1^tm1Svb/Sod1^tm1Svb Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * SJL	MGI:5529251
cn21	Sirt3^tm1.1Auw/Sirt3^tm1.1Auw Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * SJL	MGI:5556079
cn22	Cept1^tm1.1Sem/Cept1^tm1.1Sem Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * SJL	MGI:6119503
cn23	Pdxp^tm1.1Ango/Pdxp^tm1.1Ango Tg(ACTA1-cre)79Jme/0	involves: C57BL/6J * SJL	MGI:6367627
cn24	Gt(ROSA)26Sor^tm1.1(DUX4*)Plj/Gt(ROSA)26Sor^+ Tg(ACTA1-cre)79Jme/0	involves: C57BL/6 * SJL	MGI:6120562

Genotype
MGI:5305236

cn1

• Allelic Composition: Ncor1^tm1.1Ics/Ncor1^tm1.1Ics; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

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

muscle

abnormal skeletal muscle morphology ( J:178827 )

• connective tissue between muscle bundles is less abundant

• increased mitochondrial content with more abundant and larger mitochondria

abnormal skeletal muscle fiber mitochondrial morphology ( J:178827 )

• increase in the number and size of mitochondria in skeletal muscle

abnormal quadriceps morphology ( J:178827 )

• decrease in the number of the more glycolytic MyHC2b fibers and an increase in the number of more oxidative MyHC2x and 2a fibers

abnormal gastrocnemius morphology ( J:178827 )

• large sections with reddish color

• decrease in the number of the more glycolytic MyHC2b fibers and an increase in the number of more oxidative MyHC2x and 2a fibers

abnormal soleus morphology ( J:178827 )

• more intensely red

increased skeletal muscle fiber diameter ( J:178827 )

abnormal muscle physiology ( J:178827 )

• increase in mitochondrial activity in the gastrocnemius

homeostasis/metabolism

decreased susceptibility to induced hypothermia ( J:178827 )

• more cold tolerant

decreased circulating cholesterol level ( J:178827 )

• in mice on a high fat diet

decreased circulating HDL cholesterol level ( J:178827 )

• in mice on a high fat diet

decreased circulating LDL cholesterol level ( J:178827 )

• in mice on a chow or high fat diet

abnormal gas homeostasis ( J:178827 )

increased oxygen consumption ( J:178827 )

• increased on both a high fat and chow diet

decreased respiratory quotient ( J:178827 )

• marked decrease in mice on a high fat diet

abnormal aerobic fitness ( J:178827 )

• increase in the VO2 values during exercise and slight increase in the maximal ability to utilize oxygen during exercise in mice on both a chow and high fat diet

enhanced exercise endurance ( J:178827 )

• run for a longer time and greater distance before exhaustion

behavior/neurological

increased locomotor activity ( J:178827 )

• total locomotor activity is increased

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:178827 )

• increase in the number and size of mitochondria in skeletal muscle

limbs/digits/tail

abnormal quadriceps morphology ( J:178827 )

• decrease in the number of the more glycolytic MyHC2b fibers and an increase in the number of more oxidative MyHC2x and 2a fibers

abnormal gastrocnemius morphology ( J:178827 )

• large sections with reddish color

• decrease in the number of the more glycolytic MyHC2b fibers and an increase in the number of more oxidative MyHC2x and 2a fibers

abnormal soleus morphology ( J:178827 )

• more intensely red

Genotype
MGI:5292122

cn2

• Allelic Composition: Cox15^tm1.1Zev/Cox15^tm1.1Zev; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:176080 )

• in mice treated with bezafibrate

muscle

abnormal muscle fiber mitochondrial morphology ( J:176080 )

• in muscle cells

• reduced with AICAR treatment

increased variability of skeletal muscle fiber size ( J:176080 )

• in mice treated with bezafibrate

centrally nucleated skeletal muscle fibers ( J:176080 )

• in mice treated with bezafibrate

myopathy ( J:176080 )

• in mice treated with bezafibrate

cellular

abnormal muscle fiber mitochondrial morphology ( J:176080 )

• in muscle cells

• reduced with AICAR treatment

abnormal cellular respiration ( J:176080 )

• mitochondria in muscle cells exhibit increased cellular respiration compared with wild-type cells

increased mitochondrial fission ( J:176080 )

• compensatory in muscle cells

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:176080 )

• by P30, mice exhibit extremely reduced motor performance on a standard treadmill compared with wild-type mice

• treatment with AICAR does not improve motor performance

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:176080 )

• in mice treated with bezafibrate

increased physiological sensitivity to xenobiotic ( J:176080 )

• mice treated with bezafibrate exhibit increased mitochondrial myopathy, apoptosis, and lethality compared with similarly treated wild-type mice

Genotype
MGI:6118901

cn3

• Allelic Composition: Hspb7^tm1.1Yty/Hspb7^tm1.1Yty; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129 * C57BL/6J * SJL

mortality/aging

premature death ( J:246267 )

• all mice die between P1 and P60

postnatal lethality, incomplete penetrance ( J:246267 )

• mice start to die within the first week after birth

muscle

abnormal sarcomere morphology ( J:246267 )

• disorganized the diaphragm at 6 months, including sarcomeric Z- line streaming, the insertion of an additional sarcomere, and myofibrillar disorganization with focal loss of cross-striation

abnormal Z line morphology ( J:246267 )

• Z-line streaming, causing filament disruption, and Z-line disruption are observed in the diaphragm muscle

centrally nucleated skeletal muscle fibers ( J:246267 )

• at 36 weeks in diaphragm muscles

abnormal diaphragm morphology ( J:246267 )

• fibrosis at 12 weeks

• disorganized sarcomeres in the diaphragm at 6 months, including sarcomeric Z-line streaming, the insertion of an additional sarcomere, and myofibrillar disorganization with focal loss of cross-striation

• diaphragm muscle exhibits filament disruption, small rod bodies and vacuoles and central nuclei

• irreversible aggregation of filamin C and sarcoglycans

• reduced muscle mass with reduced muscle weight at 12 weeks

• however, diaphragm is normal at P1

skeletal muscle fibrosis ( J:246267 )

• in the diaphragm, but not the soleus, at 2 weeks

myopathy ( J:246267 )

• progressive

respiratory system

abnormal respiratory function ( J:246267 )

• elevated enhanced pause

abnormal forced expiratory flow rates ( J:246267 )

• increased respiratory peak expiration flow and relaxation time at lower breath frequency

homeostasis/metabolism

increased circulating creatine kinase level ( J:246267 )

• at 36 weeks

growth/size/body

decreased body weight ( J:246267 )

• after 40 weeks

behavior/neurological

decreased grip strength ( J:246267 )

• at 36 weeks with progressive myopathy

Genotype
MGI:3721894

cn4

• Allelic Composition: Smn1^tm1Jme/Smn1^tm1.1Jme; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129 * C57BL/6J * SJL

mortality/aging

premature death ( J:67884 )

• extremely reduced life expectancy, dying at a mean age of 33 days

behavior/neurological

abnormal limb posture ( J:67884 )

• in 4 weeks old mutant mice

abnormal locomotor behavior ( J:67884 )

• reduced spontaneous and induced motor activity after 3 weeks of age

paralysis ( J:67884 )

• severe muscle paralysis after 3 weeks of age

skeleton

kyphosis ( J:67884 )

• severe kyphosis after 3 weeks of age

muscle

abnormal skeletal muscle fiber morphology ( J:67884 )

• infiltration of connective tissue with mononuclear cells, and regenerating myocytes in 4-weeks-old mutant mice

• the morphology of skeletal muscle from mutant mice was similar to that of control at 3 weeks of except the presence of some rare necrotic muscle fibers surrounded by mononuclear cell infiltration

increased variability of skeletal muscle fiber size ( J:67884 )

• excessive variation in fiber size

centrally nucleated skeletal muscle fibers ( J:67884 )

• large central nuclei in 4-weeks-old mutant mice

skeletal muscle necrosis ( J:67884 )

• in 4-weeks-old mutant mice

abnormal muscle physiology ( J:67884 )

• based on immunological examination, mutant mice display destabilization of the sarcolemma indicated by increased serum creatine kinase activity, abnormal uptake of a membrane impermeant molecule, and patchy or lacking dystrophin

nervous system

nervous system phenotype ( J:67884 )

N • the morphology of motor neurons was similar to that of control and no significant loss of motor neurons of the anterior horns was detected in mutant mice at 4 weeks of age

homeostasis/metabolism

increased circulating creatine kinase level ( J:67884 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:67884

Genotype
MGI:3688083

cn5

• Allelic Composition: Actg1^tm1Erv/Actg1^tm1Erv; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

behavior/neurological

limb grasping ( J:112808 )

• about 2/3 of mice show classical hind limb contractures when suspended by the tail

• persists throughout life without getting any worse

decreased locomotor activity ( J:112808 )

• persists throughout life without getting any worse

• reduced mobility

muscle

abnormal Z line morphology ( J:112808 )

• dystrophin is less organized at the z-line in some muscles

abnormal skeletal muscle fiber morphology ( J:112808 )

• muscles primarily made up of type II fibers are most affected

increased variability of skeletal muscle fiber size ( J:112808 )

• more variability in muscle fiber size

centrally nucleated skeletal muscle fibers ( J:112808 )

• centrally nucleated fibers start appearing in muscle at about 3 months of age and progress to widespread incidence by 12 to 18 months

impaired skeletal muscle contractility ( J:112808 )

• maximal force production by extensor digitorum longus muscle is less than in controls

• maximal titanic force is similar to controls

Genotype
MGI:4881929

cn6

• Allelic Composition: Actg1^tm1.2Erv/Actg1^tm1.2Erv; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

behavior/neurological

limb grasping ( J:112808 )

• about 2/3 of mice show classical hind limb contractures when suspended by the tail

• persists throughout life without getting any worse

decreased locomotor activity ( J:112808 )

• reduced mobility

• persists throughout life without getting any worse

muscle

abnormal Z line morphology ( J:112808 )

• dystrophin is less organized at the z-line in some muscles

abnormal skeletal muscle fiber morphology ( J:112808 )

• muscles primarily made up of type II fibers are most affected

increased variability of skeletal muscle fiber size ( J:112808 )

• more variability in muscle fiber size

centrally nucleated skeletal muscle fibers ( J:112808 )

• centrally nucleated fibers start appearing in muscle at about 3 months of age and progress to widespread incidence by 12 to 18 months

impaired skeletal muscle contractility ( J:112808 )

• maximal force production by extensor digitorum longus muscle is less than in controls

• maximal titanic force is similar to controls

Genotype
MGI:5499166

cn7

• Allelic Composition: Pik3r4^tm1.1Mpnd/Pik3r4^tm1.1Mpnd; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N * SJL

muscle

increased skeletal muscle glycogen level ( J:198770 )

• as early as 2 months of age

myositis ( J:198770 )

• as early as 2 months of age

abnormal sarcolemma morphology ( J:198770 )

centrally nucleated skeletal muscle fibers ( J:198770 )

• as early as 2 months of age

skeletal muscle fiber necrosis ( J:198770 )

• as early as 2 months of age

skeletal muscle degeneration ( J:198770 )

• severe muscular degeneration (with necrotic fibers, cell infiltration and centronucleated fibers) as early as 2 months of age

• more pronounced in fast twitch muscles compared to in mice with muscle-specific knock-out of Atg7^tm1Tchi

muscle weakness ( J:198770 )

• reduced force from the gastrocnemius of mice subjected to stimulation of the sciatic nerve

myopathy ( J:198770 )

• mice display symptoms of autophagic vacuolar myopathies

cellular

abnormal autophagy ( J:198770 )

• compromised in muscles with accumulation of autophagosomes and lysosomes

homeostasis/metabolism

abnormal autophagy ( J:198770 )

• compromised in muscles with accumulation of autophagosomes and lysosomes

increased circulating creatine kinase level ( J:198770 )

• 8-fold

increased skeletal muscle glycogen level ( J:198770 )

• as early as 2 months of age

immune system

myositis ( J:198770 )

• as early as 2 months of age

Genotype
MGI:3720797

cn8

• Allelic Composition: Csnk2b^tm1.1Bb/Csnk2b^tm1.1Bb; Tg(ACTA1-cre)79Jme/?
• Genetic Background: involves: 129S2/SvPasCrl * C57BL/6J * SJL

behavior/neurological

decreased grip strength ( J:110237 )

• after 4 months grip strength decreases as measured by the amount of time they could cling upside-down to a wire grid

nervous system

abnormal neuromuscular synapse morphology ( J:110237 )

• at 6 months, mice exhibit an impaired morphological appearance of the synaptic cholinergic receptor clusters whereby clusters are spotty

abnormal miniature endplate potential ( J:110237 )

• after 4 months, miniature endplate currents reduction accompanies reduction in grip strength

growth/size/body

decreased body weight ( J:110237 )

• at 4 months, body weight is slightly reduced by 5% to 10%

Genotype
MGI:4849944

cn9

• Allelic Composition: Mtor^tm1.2Koz/Mtor^tm1.2Koz; Tg(ACTA1-cre)79Jme/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL

mortality/aging

premature death ( J:162918 )

• death between 22 and 38 weeks of age

limbs/digits/tail

abnormal limb muscle morphology ( J:162918 )

• severe reduction of plantaris muscle mass (fast-twitch)

abnormal gastrocnemius morphology ( J:162918 )

• severe reduction of fast-twitch muscle mass

abnormal soleus morphology ( J:162918 )

• slow-twitch muscle mass unaffected or slightly increased

abnormal tibialis anterior morphology ( J:162918 )

• severe reduction of fast-twitch muscle mass

• cross sectional area decreased by 24%

muscle

abnormal muscle morphology ( J:162918 )

• paler in color

• two fold reduction in mitochondrial content

increased skeletal muscle glycogen level ( J:162918 )

abnormal limb muscle morphology ( J:162918 )

• severe reduction of plantaris muscle mass (fast-twitch)

abnormal gastrocnemius morphology ( J:162918 )

• severe reduction of fast-twitch muscle mass

abnormal soleus morphology ( J:162918 )

• slow-twitch muscle mass unaffected or slightly increased

abnormal tibialis anterior morphology ( J:162918 )

• severe reduction of fast-twitch muscle mass

• cross sectional area decreased by 24%

abnormal skeletal muscle fiber morphology ( J:162918 )

centrally nucleated skeletal muscle fibers ( J:162918 )

• regenerating fibers with central nuclei

abnormal diaphragm morphology ( J:162918 )

• fibrosis

• fatty infiltration

skeletal muscle degeneration ( J:162918 )

• degeneration with phagocytosis and mononuclear cell infiltration

• inter fiber connective tissue

skeletal muscle fiber degeneration ( J:162918 )

• variable fiber size

• small atrophic fibers observed

abnormal muscle physiology ( J:162918 )

abnormal muscle contractility ( J:162918 )

• maximum tetanic and twitch force is significantly reduced in the soleus and tibialis anterior

• contractions are slow

• increased force deficit in high stress muscle-eccentric contractions of the tibialis anterior

abnormal muscle relaxation ( J:162918 )

• slow

increased muscle fatigability ( J:162918 )

• soleus is less resistant to fatigue

homeostasis/metabolism

decreased circulating glucose level ( J:162918 )

• significantly reduced whole body glucose levels in fasting mice

• normal glucose and insulin levels in fed mice

abnormal oxygen consumption ( J:162918 )

• ratio of maximal to basal respiration is increased in the soleus muscle

decreased oxygen consumption ( J:162918 )

• rate of oxygen consumption by the soleus muscle is diminished

increased skeletal muscle glycogen level ( J:162918 )

growth/size/body

decreased body weight ( J:162918 )

• body weight is reduced by 10% at 6 weeks of age

postnatal growth retardation ( J:162918 )

• growth rate starts to decrease at 4 weeks of age

cellular

decreased mitochondrial number ( J:162918 )

• two fold reduction in mitochondrial content in skeletal muscle

skeleton

kyphosis ( J:162918 )

• spinal deformity begins to develop starting around 13 weeks of age

respiratory system

decreased respiration ( J:162918 )

• difficulty breathing starting around 13 weeks of age

behavior/neurological

abnormal limb posture ( J:162918 )

• abnormal hind limb posture

Genotype
MGI:3714846

cn10

• Allelic Composition: Gabpa^tm1Sjb/Gabpa^tm1.1Sjb; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:121823 )

• mice do not exhibit any muscular or motor nerve defects; neuromuscular synapses form normally and acetycholine receptor clusters are present; transcription from synaptic nuclei also appears unaffected

Genotype
MGI:6280330

cn11

• Allelic Composition: Gt(ROSA)26Sor^tm1(DUX4)Sqh/Gt(ROSA)26Sor⁺; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL

mortality/aging

prenatal lethality ( J:268959 )

• no mutant pups are produced

Genotype
MGI:5473317

cn12

• Allelic Composition: Rxfp2^tm1Aia/Rxfp2^{tm1c(EUCOMM)Wtsi}; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * C57BL/6N * SJL

reproductive system

reproductive system phenotype ( J:194006 )

N • mice exhibit normal testis position

Genotype
MGI:5440761

cn13

• Allelic Composition: Lrp4^tm1.1Line/Lrp4^tm1.1Line; Mnx1^tm4(cre)Tmj/Mnx1⁺; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * C57BL/6J * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:188352 )

• with cyanosis

nervous system

abnormal motor neuron morphology ( J:188352 )

• increased number and length of secondary or intramuscular branches with tertiary and quaternary branches

• secondary branches are longer than in Lrp4^tm1.1Line/Lrp4^tm1.1Line Tg(ACTA1-cre)79Jme mice

• nerve terminals are fragmented in diaphragm

abnormal neuromuscular synapse morphology ( J:188352 )

• severely impaired formation

• almost undetectable in the diaphragm at E13.5

• fewer and smaller AChR clusters

homeostasis/metabolism

cyanosis ( J:188352 )

• soon after birth

Genotype
MGI:5440759

cn14

• Allelic Composition: Lrp4^tm1.1Line/Lrp4^tm1.1Line; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6J * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:188352 )

• most mice do not die until P15

• few mice survive beyond the postnatal period

nervous system

abnormal motor neuron morphology ( J:188352 )

• increased number and length of secondary or intramuscular branches with tertiary and quaternary branches

• motor axons fail to terminate at AChR clusters

• however, primary nerve branches are normal

abnormal neuromuscular synapse morphology ( J:188352 )

• abnormal AChR clusters in the diaphragm with wider area in the middle of muscle fibers, increased endplate band-width (at P0 and P10), elongated morphology, reduced average cluster size and increased cluster number

• ectopic AChR clusters

abnormal endplate potential ( J:188352 )

• decreased amplitudes of endplate potentials

abnormal miniature endplate potential ( J:188352 )

• smaller than in control mice

Genotype
MGI:3720805

cn15

• Allelic Composition: Mtm1^tm1.2Jman/Y; Tg(ACTA1-cre)79Jme/?
• Genetic Background: involves: 129T1/Sv * C57BL/6 * SJL

mortality/aging

premature death ( J:81791 )

♂ • similar phenotype compared to hemizygous male Mtm1^tm1.1Jman mice

growth/size/body

postnatal growth retardation ( J:81791 )

♂ • a very similar phenotype compared to hemizygous male Mtm1^tm1.1Jman mice showing progressive growth impairment starting at 4 weeks of age

muscle

skeletal muscle fiber atrophy ( J:81791 )

♂ • similar phenotype compared to hemizygous male Mtm1^tm1.1Jman mice, many atrophic myofibers are seen by histological analyses

centrally nucleated skeletal muscle fibers ( J:81791 )

♂ • similar phenotype compared to hemizygous male Mtm1^tm1.1Jman mice, many atrophic myofibers that contain centrally located nuclei are seen by histological analyses

myopathy ( J:81791 )

♂ • a very similar phenotype compared to hemizygous male Mtm1^tm1.1Jman mice starting at 4 weeks of age in the hindlimbs, that becomes generalized at 5 weeks

Genotype
MGI:3712148

cn16

• Allelic Composition: Gabpa^tm1Pjh/Gabpa^tm1Pjh; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

nervous system

abnormal neuromuscular synapse morphology ( J:121356 )

• 76% of soleus NMJs show less branching than controls, but appear relatively normal and are classed as type 1, while 24% of soleus NMJs show only a single ring structure (type 2); diaphragm and sternomastoid muscles show similar proportions of the two NMJ types

• type 1 soleus NMJs show increased total area and area occupied by acetylcholine receptors, but percentage of area occupied by AChRs is unchanged relative to controls; 76% increase in area occupied by AChRs corresponds to a 1.8-fold increase in number of AChRs in the synaptic region in 3 month old mice relative to controls

• type 2 soleus NMJs are of equal area to control NMJs, but show a significant decrease in percentage of area occupied by AChRs

• distribution and appearance of mitochondria, synaptic vesicles, or postsynaptic junctional folds are the same in mutant and control soleus and diaphragm muscles

abnormal PNS synaptic transmission ( J:121356 )

• amplitudes of miniature endplate currents (MEPCs) and endplate currents (EPCs) are significantly reduced at NMJs; EPCs show a significant decrease (171 uV) relative to control (277 uV)

• mean EPC amplitudes are similar to MEPC amplitudes in controls

abnormal channel response ( J:121356 )

• decay constants, a measure of channel opening time, are significantly longer at soleus and diaphragm NMJs of mutants at 3 months of age, compared to controls; decay constants range from 100-150 mseconds in mutants compared to 30-40 mseconds for controls

abnormal synaptic acetylcholine release ( J:121356 )

• spontaneous and evoked transmitter release at the NMJ is reduced relative to controls

decreased neurotransmitter release ( J:121356 )

• mean quantal content is significantly lower at mutant NMJs than in controls

muscle

muscle phenotype ( J:121356 )

N • no differences in growth and development of skeletal muscle is seen between mutant and control, non-transgenic mice between 1 and 6 months of age; no gait abnormalities result from any muscular abnormalities

N • electrophysiological alterations do not result in significant changes in fatigability (at 1 year) or strength (from 1-6 months)

Genotype
MGI:7647260

cn17

• Allelic Composition: Ar^tm2Ska/Ar^tm2Ska; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj * SJL

behavior/neurological

decreased grip strength ( J:316008 )

♀ • 9-week-old females implanted with a biodegradable pellet containing 10 mg dihydrotestostorone (DHT) to induce muscle hypertrophy do not show an increase in grip strength as is seen in wild-type mice with the DHT pellet

♀ • however, body weight and skeletal muscle weight are increased by DHT treatment to the same extent as in wild-type mice indicating decreased muscle strength

Genotype
MGI:7378413

cn18

• Allelic Composition: Acad9^{tm1c(KOMP)Wtsi}/Acad9^{tm1c(KOMP)Wtsi}; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/N * SJL

muscle

abnormal muscle morphology ( J:326969 )

• mice show some disruption of normal muscle architecture with presence of abnormal myofibril bundles and centralized nuclei, indicative of persistent muscle damage

centrally nucleated skeletal muscle fibers ( J:326969 )

muscle weakness ( J:326969 )

• no mice successfully complete the hanging wire test, with 50% of mice falling just after 60 seconds and the longest hanging time is just over 100 seconds compared to wild-type mice that can hang for 3 minutes and mice are inactive for 15-30 min after falling from the hanging wire

behavior/neurological

impaired exercise endurance ( J:326969 )

• no mice successfully complete the hanging wire test, with 50% of mice falling just after 60 seconds and the longest hanging time is just over 100 seconds compared to wild-type mice that can hang for 3 minutes indicating impaired exercise tolerance

• mice are inactive for 15-30 min after falling from the hanging wire unlike wild-type mice which return to normal activity immediately after the test

homeostasis/metabolism

impaired exercise endurance ( J:326969 )

• no mice successfully complete the hanging wire test, with 50% of mice falling just after 60 seconds and the longest hanging time is just over 100 seconds compared to wild-type mice that can hang for 3 minutes indicating impaired exercise tolerance

• mice are inactive for 15-30 min after falling from the hanging wire unlike wild-type mice which return to normal activity immediately after the test

lactic acidosis ( J:326969 )

• mice exhibit higher resting L-lactic acid levels, more than double that of wild-type levels, and have over double the wild-type levels at the time of fall in the hanging wire test

• however, glucose levels are normal before and after the hanging wire test

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nuclear type mitochondrial complex I deficiency 20		DOID:0112072	OMIM:611126	J:326969

Genotype
MGI:5316090

cn19

• Allelic Composition: Cfl2^tm1Itl/Cfl2^tm1Itl; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * C57BL/6NTac * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:182571 )

• mice die between P7 and P12

muscle

abnormal sarcomere morphology ( J:182571 )

• muscle fibers exhibit intact sarcomeres alongside disrupted ones unlike in wild-type mice

abnormal skeletal muscle morphology ( J:182571 )

• accumulation of F-actin

abnormal skeletal muscle fiber morphology ( J:182571 )

• muscle fibers exhibit intact sarcomeres alongside disrupted ones unlike in wild-type mice

Genotype
MGI:5529251

cn20

• Allelic Composition: Sod1^tm1Svb/Sod1^tm1Svb; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * SJL

muscle

muscle phenotype ( J:201098 )

N • mice do not exhibit functional denervation

N • muscles exhibit normal mitochondrial function, reactive oxygen species generation, redox status and heat-shock response

increased extensor digitorum longus weight ( J:201098 )

• at 16 to 17 months

increased quadriceps weight ( J:201098 )

• at 16 to 17 months

increased gastrocnemius weight ( J:201098 )

• at 6 months and 16 to 17 months

increased soleus weight ( J:201098 )

• at 16 to 17 months

increased tibialis anterior weight ( J:201098 )

• at 16 to 17 months

centrally nucleated skeletal muscle fibers ( J:201098 )

• remains constant throughout life

increased skeletal muscle mass ( J:201098 )

• for a variety of muscles at 6 months and 16 to 17 months

abnormal muscle physiology ( J:201098 )

• ongoing, focal degeneration-regeneration

abnormal muscle regeneration ( J:201098 )

• ongoing, focal degeneration-regeneration

muscle weakness ( J:201098 )

behavior/neurological

behavior/neurological phenotype ( J:201098 )

N • mice exhibit normal performance on a rotarod

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:201098 )

N • mice exhibit normal performance on a treadmill

nervous system

nervous system phenotype ( J:201098 )

N • mice do not exhibit functional denervation

limbs/digits/tail

increased extensor digitorum longus weight ( J:201098 )

• at 16 to 17 months

increased quadriceps weight ( J:201098 )

• at 16 to 17 months

increased gastrocnemius weight ( J:201098 )

• at 6 months and 16 to 17 months

increased soleus weight ( J:201098 )

• at 16 to 17 months

increased tibialis anterior weight ( J:201098 )

• at 16 to 17 months

Genotype
MGI:5556079

cn21

• Allelic Composition: Sirt3^tm1.1Auw/Sirt3^tm1.1Auw; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * SJL

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207274 )

N • mice fed chow or a high-fat diet exhibit a normal metabolic phenotype

Genotype
MGI:6119503

cn22

• Allelic Composition: Cept1^tm1.1Sem/Cept1^tm1.1Sem; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * SJL

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:249456 )

N • circulating metabolite levels when fed high fat diet

N • insulin suppression of endogenous hepatic glucose production (HGP suppression) high fat diet fed mice

N • serum free fatty acids, adiponectin and leptin concentrations high fat diet fed mice

N • metabolic rate of high fat diet fed mice

N • body temperature during cold tolerance test of high fat diet fed mice

decreased circulating glucose level ( J:249456 )

• after insulin administration when fed high fat diet

increased respiratory quotient ( J:249456 )

• during dark cycle when fed high fat diet

improved glucose tolerance ( J:249456 )

• when fed high fat diet

• increase in insulin-stimulated 2-deoxyglucose (2DG) uptake by soleus muscles isolated from high fat diet fed mice

increased insulin sensitivity ( J:249456 )

• lower blood glucose after insulin administration when fed high fat diet

• twofold greater glucose infusion rate in hyperinsulinemic-euglycemic clamp tests of high fat diet fed mice

• twofold greater insulin-stimulated glucose disposal rate (IS-GDR) in hyperinsulinemic-euglycemic clamp tests of high fat diet fed mice

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:249456 )

• decreased performance (running time and distance) of high fat diet fed mice during high-intensity exercise tests

decreased grip strength ( J:249456 )

• in forelimbs of high fat diet fed mice

cellular

cellular phenotype ( J:249456 )

N • protein content of mitochondrial respiration complex I-V, gene expression of mitochondrial biogenesis markers and levels of fatty acid oxidation in gastrocnemius muscles of high fat diet fed mice

N • diacylglycerol (DAG) content, ATP content and mitochondrial density (as determined by electron microscopy) in muscles of high fat diet fed mice

abnormal cellular respiration ( J:249456 )

• reduced phosphatidylethanolamine (PE) in sarcoplasmic reticulum of gastrocnemius muscles of high fat diet fed mice

• increased levels of several phosphatidylcholine (PC) species in sarcoplasmic reticulum of gastrocnemius muscles of high fat diet fed mice

• reduced sarco/endoplasmic Ca2+ ATPase (SERCA) activity in sarcoplasmic reticulum of gastrocnemius muscles of high fat diet fed mice

muscle

muscle weakness ( J:249456 )

• in forelimbs of high fat diet fed mice

• decreased running time and distance of high fat diet fed mice during high-intensity exercise tests

growth/size/body

growth/size/body region phenotype ( J:249456 )

N • body weight and composition, tissue weights when fed high fat diet

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:249456 )

N • hormones levels when fed high fat diet

Genotype
MGI:6367627

cn23

• Allelic Composition: Pdxp^tm1.1Ango/Pdxp^tm1.1Ango; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6J * SJL

behavior/neurological

increased grip strength ( J:270551 )

• hind paw grip strength is increased in older mice

Genotype
MGI:6120562

cn24

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(DUX4*)Plj}/Gt(ROSA)26Sor⁺; Tg(ACTA1-cre)79Jme/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

perinatal lethality ( J:256652 )

• pups are stillborn and small

• pups develop until almost full term (E19.5)

limbs/digits/tail

abnormal limb morphology ( J:256652 )

• E16.5 embryos exhibit deformed limbs

growth/size/body

decreased fetal size ( J:256652 )

• observed in E16.5 embryos

nervous system

abnormal spinal cord morphology ( J:256652 )

• E16.5 embryos exhibit aberrant spinal columns

skeleton

small thoracic cage ( J:256652 )

• E16.5 embryos exhibit underdeveloped rib cages