Phenotypes Associated with This Genotype

Genotype
MGI:3789953

• Allelic Composition: Tg(ACTA1-MYOT*T57I)71Mah/?
• Genetic Background: involves: C57BL/6 * SJL

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

muscle

diffuse Z line ( J:110377 )

• broadening of Z-discs occurs in older mice

• Z-discs can subsequently merge into streaming bodies involving multiple Z-discs

abnormal skeletal muscle morphology ( J:110377 )

• transgene expression of human myotilin containing a point mutation occurs in skeletal muscle

• level of transgene expression is 2.6 fold higher than endogenous mouse myotilin

abnormal skeletal muscle fiber morphology ( J:110377 )

• mice develop dense and irregular myofibrillar aggregates in the quadriceps, triceps, and the extensor digitorum longus (EDL) muscles

• myofibrillar aggregates are often associated with autophagic vesicles

• the aggregations are progressive with age starting at 2 weeks when small focal points of aggregation are detectable

• aggregates expand up to 40 micrometers and will often occupy the entire cross-sectional area of the myofibers of older mice

• the proportion of myofibers containing aggregates is 11-12% at 6 months and 17-18.2% at 12 months of age

skeletal muscle interstitial fibrosis ( J:110377 )

• fibrosis and adipose infiltration are associated with the myofibrillar aggregates that occurs in older mice

dystrophic muscle ( J:110377 )

• 8-10 month old mice have 33% less mass in their EDL muscle than in wild-types

• the cross sectional area of the EDL myofibers is reduced to a similar degree

impaired skeletal muscle contractility ( J:110377 )

• the specific maximum force of the EDL muscle from 8-10 month old male mice is reduced by 24% and the maximum isometric force is reduced by 46%

muscle weakness ( J:110377 )

• muscle contractility of the EDL muscle from 8-10 month old mice is substantially reduced

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myofibrillar myopathy 3		DOID:0080094	OMIM:609200	J:110377