This gene trap mutation abolishes endogenous Lrsam1 gene function while expressing a B-geo reporter fusion protein from the disrupted locus. Mutant mice may be useful as a lacZ reporter for Lrsam1 expression or as a knockout model for studying the endosome-lysosome sorting pathway, and peripheral neuropathies, in particular Charcot-Marie-Tooth disease.
Robert Burgess, The Jackson Laboratory
Lrsam1 or RIFLE (leucine rich repeat and sterile alpha motif containing 1) encodes an E3 ubiquitin ligase involved in the endosome to lysosome sorting pathway. It is associated with the axonal neuropathy, Charcot-Marie-Tooth disease type 2 (CMT2). Lrsam1 is expressed in the motor neurons of the ventral horn, cell bodies of peripheral sensory neurons in the dorsal root ganglia (DRG) and to a lessor extent in the brain stem.
Homozygous mice are viable, fertile and exhibit mild neuromuscular junction and axonal defects with the number of axons slightly reduced in the sensory and motor branches of the femoral nerve. In response to challenge with the neurotoxic agent acrylamide, mice show increased sensitivity and more rapid motor axon degeneration.
Mice heterozygous for the mutation exhibit a wider stance and turn their paws outward, however, gait is unimpaired.
This strain may be useful for studying peripheral neuropathies, in particular Charcot-Marie-Tooth disease.
Bay Genomics gene trap embryonic stem (ES) cell line RRK461, derived from 129P2/OlaHsd and expressing B-geo (a fusion of B-galactosidase and neomycin phospotransferase II), was sequenced to locate the Lrsam1 gene trap insertion site at position 1149 of intron 22. ES cells were cultured and microinjected into blastocysts. Resultant chimeras were backcrossed to C57BL/6J for at least 5 generations by the donating laboratory. Western blot analysis demonstrates an absence of protein in mutants.
|Allele Name||gene trap RRK461, BayGenomics|
|Allele Type||Gene trapped|
|Gene Symbol and Name||Lrsam1, leucine rich repeat and sterile alpha motif containing 1|
|Site of Expression||LacZ is expressed in place of the abolished endogenous Lrsam1 gene function in the motor neurons of the ventral horn, cell bodies of peripheral sensory neurons in the dorsal root ganglia and to a lessor extent in the brain stem.|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The gene trap vector, RRK461, inserted at position 1149 of intron 22. Western blot analysis confirms the absence of protein expression.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6.129P2-Lrsam1Gt(RRK461)Byg/RwbMmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36934 in your Materials and Methods section.