B6.C3(Cg)-Rora^sg/J

Stock number: 002651
Product name: B6-staggerer
Research areas: Neurobiology Research

Description

The cerebellar cortex of homozygous mutant staggerer (Rora^sg) mice show a deficiency of granule cells and Purkinje cells. They have a staggering gait, mild tremor, and hypotonia. These mice may be useful in studies of the composition and function of granule cells.

Detailed description

Mice homozygous for the staggerer spontaneous mutation (Rora^sg) show a staggering gait, mild tremor, hypotonia, and small size. The cerebellar cortex of homozygous mutant mice is grossly underdeveloped with a deficiency of granule cells and Purkinje cells. The remaining granule cells migrate inward from the external layer prematurely and then degenerate. Purkinje cells are much delayed in postnatal differentiation and lack the dendritic spines on which synapses with the parallel fibers from the granule cells normally occur. Staggerer mutant mice have been used as a source of an agranulate cerebellum in a number of investigations of the composition and function of granule cells. Kopmels et al. have reported a hyperproduction of IL1 biological activity and mRNA from LPS stimulated spleen cells of Rora^sg/Rora^sg mice on the C57BL/6J background relative to wild type siblings. In addition, homozygous mice exhibit an enhanced susceptibility to LPS-induced lung inflammation, suggesting a role for Rora in LPS-induced inflammatory responses (Stapleton CM, et al., 2005).

Development

The first Rora^sg/Rora^sg mouse was observed in 1955 among the F2 progeny of a (BALB/cHm x C3H/HeJ)F1 female and a male of an obese(Lep^ob) stock of mixed background. The mutation was maintained for several generations by an intercross-backcross (within the same or a parallel lineage) mating scheme, then was backcrossed onto C57BL/6J for four generations. A Rora^sg/+ male from the fourth backcross was mated to a female C57BL/10-Myo5a^d Bmp5^se mouse to introduce the dilute and short-ear mutations into the stock in repulsion with Rora^{6 sg} ; this allowed the heterozygotes (Rora^sg + +/+ Myo5a^d Bmp5^se to be identified by a lack of either recessive phenotype. Brother-sister inbreeding was continued. At F55, Myo5a^d Bmp^se was backcrossed onto C57BL/6J seven times; at F58, Rora^sg was backcrossed onto C57BL/6J four times. The Rora^sg + +/+ Myo5a^d Bmp5^se stock was then reconstructed by crossing mice of the two independent stocks and maintained by brother-sister inbreeding. In early 1997, Myo5a^d and Bmp5^se were bred out of the stock by selective breeding assisted by PCR testing. Based on the alleles carried by this strain for 16 SSLPs mapping within 1 cM of Rora, it appears that the mutation occurred on a C3H chromosome (Hamilton et al. 1996).

Allele

Symbol: Rora^sg
Name: staggerer
MGI accession ID: MGI:1857035
Generation method: Spontaneous
Marker symbol: Rora
Marker name: RAR-related orphan receptor alpha
Chromosome: 9
Strain of origin: obese stock
Molecular note: This allele contains a 6.5kb genomic deletion of an exon encoding part of the ligand binding domain. The deletion results in an exon-skipping event that introduces a shift in the reading frame. The resulting protein is predicted to be truncated due to introduction of a premature stop codon.