These mice carry a spontaneous mutation at the Sil1 locus characterized by adult-onset ataxia with cerebellar Purkinje cell loss. They nay be useful in studies of Alzheimer and Parkinson diseases.Read More +
Homozygous woozy (Sil1wz) mice develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations reminiscent of protein inclusions in both the ER and the nucleus. In addition, upregulation of the unfolded protein response, suggestive of ER stress, occurs in mutant Purkinje cells. The wz mutation disrupts the gene Sil1 that encodes an adenine nucleotide exchange factor of BiP, a crucial ER chaperone. Thus, perturbation of ER chaperone function in terminally differentiated neurons leads to protein accumulation, ER stress and subsequent neurodegeneration.
The woozy mutation arose spontaneously in the recombinant inbred strain CXB5/ByJ (stock #000355) and has been maintained on this background through sibling inbreeding.
|Gene Symbol and Name||Sil1, endoplasmic reticulum chaperone SIL1 homolog (S. cerevisiae)|
|Strain of Origin||CXB5/ByJ|
|Molecular Note||Mutant transcripts demonstrate splicing between exon 7 of Sil1 and an ETn retrotransposon inserted between position 4,799 and 4,800. The chimeric transcript has an in-frame stop codon after 96 nucleotides of ETn sequence.|