Phenotypes associated with this allele

• Allele Symbol: Dtna^tm1Jrs
• Allele Name: targeted mutation 1, Joshua R Sanes
• Allele ID: MGI:2148537
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dtna^tm1Jrs/Dtna^tm1Jrs	B6;129-Dtna^tm1Jrs/J	MGI:7615074
hm2	Dtna^tm1Jrs/Dtna^tm1Jrs	involves: 129X1/SvJ * C57BL/6	MGI:2176869
cx3	Dtna^tm1Jrs/Dtna^tm1Jrs Utrn^tm1Jrs/Utrn^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ	MGI:2176888
cx4	Dmd^mdx/Y Dtna^tm1Jrs/Dtna^tm1Jrs Utrn^tm1Jrs/Utrn^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn	MGI:2176891
cx5	Dtna^tm1Jrs/Dtna^tm1Jrs Dtnb^Gt(OST109050)Lex/Dtnb^Gt(OST109050)Lex	involves: 129S5/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:3621490
cx6	Dmd^mdx/Y Dtna^tm1Jrs/Dtna^tm1Jrs	involves: 129X1/SvJ * C57BL/10ScSn	MGI:2176892

Genotype
MGI:7615074

hm1

• Allelic Composition: Dtna^tm1Jrs/Dtna^tm1Jrs
• Genetic Background: B6;129-Dtna^tm1Jrs/J

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

behavior/neurological

impaired coordination ( J:338249 )

♂ • at 4 months of age, male homozygotes show reduced mean latencies to fall in a rotarod test; older males exhibit an even greater reduction

Genotype
MGI:2176869

hm2

• Allelic Composition: Dtna^tm1Jrs/Dtna^tm1Jrs
• Genetic Background: involves: 129X1/SvJ * C57BL/6

muscle

myocardial fiber degeneration ( J:59675 )

• degeneration of myocytes

cardiomyopathy ( J:59675 )

• 61% exhibit mild cardiomyopathy at 1 month, including mononuclear-cell infiltration and fibrosis, associated with plaques that are scattered through both ventricles, however hearts are not dilated or hypertrophic

dystrophic muscle ( J:59675 , J:60776 )

• develop mild skeletal dystrophy by 1 month of age; see small groups of degenerating myofibers and infiltrating monocytes (J:59675)

• the diaphragm is the most severely affected skeletal muscle (J:59675)

• muscle fibers are less structurally compromised than in Dmd^mdx mice and appear to maintain the dystrophin-containing glycoprotein complex (J:59675)

• about 40% of fibers are dystrophic (J:60776)

cardiovascular system

myocardial fiber degeneration ( J:59675 )

• degeneration of myocytes

cardiac fibrosis ( J:59675 )

cardiomyopathy ( J:59675 )

• 61% exhibit mild cardiomyopathy at 1 month, including mononuclear-cell infiltration and fibrosis, associated with plaques that are scattered through both ventricles, however hearts are not dilated or hypertrophic

nervous system

abnormal neuromuscular synapse morphology ( J:60776 )

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

• derangement of the postsynaptic membrane, with a 50% reduction in the density of junctional folds and altered distribution of electron-dense material

• postsynaptic apparatus is fragmented into discrete boutons

behavior/neurological

impaired coordination ( J:106640 )

• single knockout mutants perform more poorly than controls but better than double knockouts with Dtnb^{Gt(OST109050)Lex}

decreased grip strength ( J:106640 )

• single knockout mutants perform more poorly than controls but better than double knockouts with Dtnb^{Gt(OST109050)Lex}

Genotype
MGI:2176888

cx3

• Allelic Composition: Dtna^tm1Jrs/Dtna^tm1Jrs; Utrn^tm1Jrs/Utrn^tm1Jrs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

muscle

cardiomyopathy ( J:59675 )

• mild cardiomypathy

dystrophic muscle ( J:59675 )

• exhibit a mild skeletal dystrophy that is similar to that of single homozygous Dtna mice

cardiovascular system

cardiomyopathy ( J:59675 )

• mild cardiomypathy

nervous system

abnormal neuromuscular synapse morphology ( J:60776 )

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

• subset of synapses (20-30%) are more severely disrupted than in single Dtna mutants, with the normal branching morphology of acetylcholine receptors replaced with coarse striations radiating in a zebra stripe-like pattern

• almost complete lack of junctional folds in the postsynaptic membrane

• cultured myotubes show defects in acetylcholine clustering

Genotype
MGI:2176891

cx4

• 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:3621490

cx5

• Allelic Composition: Dtna^tm1Jrs/Dtna^tm1Jrs; Dtnb^{Gt(OST109050)Lex}/Dtnb^{Gt(OST109050)Lex}
• Genetic Background: involves: 129S5/SvEvBrd * 129X1/SvJ * C57BL/6

behavior/neurological

impaired coordination ( J:106640 )

• mutants have significantly decreased performance in ability to balance on a small platform, to hang from an inverted screen, or to balance on a rotating rod at constant or accelerating speeds

decreased grip strength ( J:106640 )

• double mutants have significantly poorer performance in a forelimb grip strength test

nervous system

abnormal CNS synapse formation ( J:106640 )

• in double knockouts, inhibitory synapse formation in the cerebellum is defective

Genotype
MGI:2176892

cx6

• 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