Mouse Models: Dysf-/- (B6.129-Dysftm1kCAM/J)

Dysf-/- mice (B6.129-Dysftm1Kcam/J)

Availability:
The Jackson Laboratory
Stock number: 013149
Strain information: http://jaxmice.jax.org/strain/013149.html
Phone: 800-422-MICE (800-422-6423)
610 Main Street, Bar Harbor, Maine 04609 USA

Mutant Mouse Regional Resource Centers (MMRRC)
Stock number: 010317-MU/H
Strain information: http://www.mmrrc.org/strains/10317/010317.html
Phone: 800-910-2291 or 207-288-6009

Development:
A targeting vector containing a neomycin resistance gene was use to replace a 12 kb region containing the last three coding exons of the gene, including the exons coding for the transmembrane domain. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts.  This strain was backcrossed to C57BL/6 for seven generations by the donating laboratory.     

Mutation:
A 12-kb region of the genome, containing the last three exons (Exons 53-55, aa1983-2080) of dysferlin, is deleted. This deletion removes the transmembrane domain of the protein. The mice are of a mixed 129SvJ and C57BL/6 background and are homozygous for this deletion.

Symptoms:
By the age of 2 months, a few individual necrotic and centrally nucleated fibers can be detected throughout the muscle; the number increases with age. By 8 months, the muscle develops all of the pathological characteristics of muscular dystrophy (e.g. regenerating fibers, split fibers, muscle necrosis with macrophage infiltration and fat replacement). The severity of the pathology varies in different muscles. Muscle fibers are defective in Ca2+-dependent sarcolemma resealing/repair. No protein product from the targeted gene is detected in skeletal muscle microsomes.

Comparison with other disease strains:
Disease progression is similar to SJL/J, Dysf-/- (Brown), and C57BL/10.SJL mice, and “faster” than in A/J mice.

Control strain(s):
C57BL/6 (for homozygotes); littermates (for heterozygotes).

References:
Bansal D, et al. 2003. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 432:168-172.