Mouse Genome Informatics
involves: C57BL/6 * SJL
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• broadening of Z-discs occurs in older mice
• Z-discs can subsequently merge into streaming bodies involving multiple Z-discs
• 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
• 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
• fibrosis and adipose infiltration are associated with the myofibrillar aggregates that occurs in older mice
• 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
• 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 contractility of the EDL muscle from 8-10 month old mice is substantially reduced

Mouse Models of Human Disease
Muscular Dystrophy, Limb-Girdle, Type 1A; LGMD1A 159000 J:110377
Myopathy, Myofibrillar, 3; MFM3 609200 J:110377
Myopathy, Spheroid Body 182920 J:110377