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.

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.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.