Phenotypes Associated with This Genotype

Genotype
MGI:5767290

• Allelic Composition: Tg(Ckm-DNAJB6_ib*F93L)#Ccwe/0
• Genetic Background: B6.Cg-Tg(Ckm-DNAJB6_ib*F93L)#Ccwe

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

mortality/aging

premature death ( J:226488 )

• about 30% of mice die within the first 40 days due to profound muscle weakness

behavior/neurological

decreased grip strength ( J:226488 )

• mice are weaker in the inverted wire screen holding test and in the grip strength test

muscle

abnormal muscle fiber morphology ( J:226488 )

• alterations in myofibrillar organization, enlarged and swollen mitochondria and autophagic/lysosomal vacuoles

• large desmin inclusions in some myofibers

• muscle shows the presence of keratin 18 positive inclusions that colocalize with the mutant protein in the center of some muscle fibers

• accumulation of the RNA-binding proteins hnRNPA1 and hnRNPA2/B1as small puncta within the center of scattered myofibers, indicating inclusions

abnormal Z line morphology ( J:226488 )

• alterations in expression and localization of Z-disc components and decreased organization

• levels of Z-disc proteins desmin, alpha-actinin, and syncolin are increased, while myotilin is unchanged and synemin is decreased

progressive muscle weakness ( J:226488 )

• mice develop progressive muscle weakness that is detectable at 2 months of age

myopathy ( J:226488 )

• mice exhibit myopathic features with internal nuclei, variation in fiber size and increased endomysial connective tissue

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant limb-girdle muscular dystrophy type 1		DOID:0110305	OMIM:603511	J:226488