B10.SJL-Dysf^im/AwaJ

Stock number: 011128
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

This spontaneous mutation of the dysferlin (Dysf) gene displays progressive muscle weakness and may be useful as a model of limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy.

Detailed description

Mice that are homozygous for this mutation exhibit a progressive muscular dystrophy characterized by myofiber degeneration and increased fibrosis. Disease onset on the C57BL/10 background is apparent by 4 weeks of age and is severe by 8 months of age, although, mice can survive until 19 months. During the late stage of the disease muscles exhibit fatty and fibrotic tissue as well as inflammatory cells. Affected muscles include the proximal limbs, (quadriceps femoris and triceps brachii) and abdominals. The distal limbs, (gastocnemius, soleus, and tibialis anterior), diaphram, and biceps brachii appear to be only mildly affected even in the late stages of the disease. Both pyruvate and creatinine kinase levels are increased. Regeneration following notexin-induced muscle damage is impaired by delayed removal of necrotic fibers and an extended inflammatory period. This mutant mouse strain may be useful as a model of limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy.

Development

The inflammatory myopathy (im) mutation arose spontaneously in the SJL inbred strain. The mutation was introgressed into C57BL/10ScSnHim for a minimum of 10 generations in the laboratory of Dr. Reginald Bittner at the Medical University of Vienna. Mice from this colony were transferred to Dr. Amy Wagers at the Joslin Diabetes Center and maintained by sibling matings. Dr. Wagers donated the strain to The Jackson Laboratory in 2010. Upon arrival, mice were bred to C57BL/10J for at least 1 generation to establish the colony.

Allele

Symbol: Dysf^im
Name: inflammatory myopathy
MGI accession ID: MGI:1857883
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Dysf
Marker name: dysferlin
Chromosome: 6
Strain of origin: SJL
Molecular note: The molecular basis for the mutation is due to a splicing mutation in the gene, resulting from a 141 bp deletion of a small tandem repeat in an intron. This splicing mutation results in the deletion of an exon from the encoded mRNA. This results in a 171 bp in-frame deletion in the encoded mRNA, and is predicted to remove 57 amino acids from the corresponding protein. This region corresponds to most of the fourth C2 domain of the protein, and the deletion likely results in instability of the protein.