Homozygous mice are viable and fertile and do not display any gross physical or behavioral abnormalities. Mutant mice exhibit no transcript splicing defects. Cre-mediated recombination of the loxP-flanked sequences results in deletion of exon 7 of the endogenous gene. As mutations of this exon are implicated in 95% of all human spinal muscular atrophy (SMA), these mice may be useful in studying SMA or other neuromuscular degenerative diseases.
For example, when crossed to a strain expressing Cre recombinase in straited muscle fibers of the somites and heart (see Stock No. 005936), this mutant mouse strain exhibits abnormal muscle fiber morphology and physiology.
Importation of this model was supported by the Spinal Muscular Atrophy Foundation. Creation and development was supported by the National Institute of Health and Medical Research of France (Inserm) and the Association Française contre les Myopathies (AFM). Additional support was provided by Families of SMA (U.S.A.) and Andrew?s Buddies (U.S.A.).
A targeting vector was used to insert a neomycin resistance gene within intron 6 and place loxP sites immediately flanking exon 7 of the endogenous gene. This construct was electroporated into “129Sv” embryonic stem (ES) cells. Correctly targeted cells were injected into blastocysts. The resulting chimeric males were bred to C57BL/6J females. Heterozygous offspring were bred to generate homozygous mice. Homozygotes on this mixed B6;129 background were bred together for approximately 5 years before arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Judith Melki|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Smn1, survival motor neuron 1|
|Strain of Origin||129|
|Molecular Note||A floxed exon 7 and neomycin resistance cassette were introduced to the gene via homologous recombination. The floxed exon 7 and neo cassette do not appear to interfere with transcript splicing in mutant animals as determined by RT-PCR analysis.|
|Mutations Made By|| |
Judith Melki, Inserm and University of Paris 11