Lama2<dy-8J>:A new remutation to dystrophia muscularis

Lama2^dy-8J: A new remutation to dystrophia muscularis

Authors: Belinda Harris, Debra Thompson, Patricia F.Ward-Bailey, Louise Dionne, Kenneth R.Johnson, Roderick T. Bronson

Source of Support: The research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resources (M.T.Davisson,PI) and Cancer Center Core Grant CA34196.

Mutation (allele) symbol: Lama2^dy-8J

Mutation (allele) name: dystrophia muscularis 8 Jackson

Gene symbol: Lama2 ^dy-8J

Strain of origin: C57BL/6J

Current strain name: C57BL/6J-Lama2^dy-8J/J

Stock #: 009692 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: neuromuscular

Abstract

We have identified a new remutation to dystrophia muscularis (Lama2dy). Mice affected by the new dy-8J mutation have rear limb paralysis first noticeable at about two weeks of age, which progresses to death usually by three to four weeks of age. A direct test for allelism was set up by mating a mouse carrying the dystrophia muscularis 2 Jackson mutation to a mouse carrying this new mutation and allelism was confirmed.

Origin and Description

This remutation was first discovered by Lisa Weaver at The Jackson Laboratory in a colony of inbred C57BL/6J mice and was recognized by its smaller size and the dragging action of its hindlimbs.

Genetic Analysis

A direct test for allelism was set up by mating a B6.WK-Lama2^dy-2J heterozygote to a new mutant heterozygote.This mating produced 25 progeny of which 6 were affected with the dystrophia muscularis phenotype confirming allelism. Using standard mapping techniques, affected mice from an intercross to CAST/EiJ were typed with markers on Chromosome 10, D10Mit52 (NCBI 37 position 33.4 Mb) and D10Mit213 (NCBI 37 position 20.1 Mb) ), in the region where dystrophia muscularis maps (NCBI 37 position 26.7 Mb) . There was no recombination with either marker, further confirming allelism.

Pathology

The eyes of two homozygous affected animals were examined with an opthalmoscope and the results were ambiguous. ERGs done on affected mice at three weeks of age showed abnormal rods and cones, but eyes were sent for histological examination and were found to be normal.

Two homozygotes and two controls were tested for auditory brain stem response (ABR) at twenty days of age. Homozygotes showed elevated thresholds 10-30 decibels above those of heterozygous controls, similar to results obtained in a previously published study of hearing loss in Lama2^dy mice (Pillers et al., 2002). A standard pathological screen of one female and one male homozygote showed the female having myopathy with rowing of nuclei in the muscle fibers and pale staining areas in lumbar roots, and the male with severe myopathy in some muscles and some muscle with very immature fibers. This is consistent with previously reported histology of the dystrophia muscularis mutations.

Acknowledgements

The authors thank Norm Hawes and Ron Hurd for eye analysis, Coleen Kane for pathological preparations, and Chantal Longo Guess for ABR analysis.

References

Pillers DA, Kempton JB, Duncan NM, Pang J, Dwinnell SJ, Trune DR. Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy. Mol Genet Metab. 2002 Jul;76(3): 217-24.

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