Wabbler-lethal (wl) is spontaneous, recessive mutation discovered in 1952 at The Jackson Laboratory. Mice homozygous for the mutation can be identified at 12 days of age by an abnormal wobbly gait, small body size, a hind limb clasping reflex, and a pronounced tremor when walking. Twenty percent of mice die by 65 days, and 100% by 130 days. In 2012, the mutation was determined to be a 21 bp deletion in exon 22 of the Atp8a2 (ATPase, aminophospholipid transporter-like, class I, type 8A, member 2) gene. Atp8a2 encodes a member of the P4 ATPase family of proteins and has phosphatidylserine translocase (flippase) activity. ATP8A2 is involved in lipid flipping, specifically, the localization of phosphatidylserine to the inner leaflet of the plasma membrane. Homozygous wl mice develop a progressive, distal axonopathy resulting in degeneration of the central and peripheral nervous system. The axonopathy is characterized by chromatolysis in the lateral and medial cerebellar nucleus, lateral vestibular nucleus, and spinal ventral horn. Cell loss is not observed. Dystrophic axons are present in the corticospinal tract, spinalcerebellar tract, retinal ganglion cells, and spinal white matter. Distal axonal degeneration is observed in the femoral and sciatic nerves. This strain may be useful in studies of axonal degeneration.
