The cerebellar cortex of homozygous mutant staggerer (Rorasg) 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.Read More +
Mice homozygous for the staggerer spontaneous mutation (Rorasg) 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 Rorasg/Rorasg 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).
The first Rorasg/Rorasg mouse was observed in 1955 among the F2 progeny of a (BALB/cHm x C3H/HeJ)F1 female and a male of an obese(Lepob) 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 Rorasg/+ male from the fourth backcross was mated to a female C57BL/10-Myo5ad Bmp5se mouse to introduce the dilute and short-ear mutations into the stock in repulsion with Rora6 sg ; this allowed the heterozygotes (Rorasg + +/+ Myo5ad Bmp5se to be identified by a lack of either recessive phenotype. Brother-sister inbreeding was continued. At F55, Myo5ad Bmpse was backcrossed onto C57BL/6J seven times; at F58, Rorasg was backcrossed onto C57BL/6J four times. The Rorasg + +/+ Myo5ad Bmp5se stock was then reconstructed by crossing mice of the two independent stocks and maintained by brother-sister inbreeding. In early 1997, Myo5ad and Bmp5se 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 Synonym(s)||RORalpha-; sg|
|Gene Symbol and Name||Rora, RAR-related orphan receptor alpha|
|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.|
Rorasg/Rorasgmice can be identified by 10-15 days of age by their poor locomotor coordination, lurching movements and frequent falls; homozygotes as young as three days can be distinguished by behavioral testing (Heuze et al.1997). Homozygotes die between two to three weeks of age. Due to their early and high mortality, homozygous mutant mice are not available from our colony. In some cases, the homozygote lifespan can be extended by adding crushed grain to the bottom of the cage and keeping pups with a lactating female. As heterozygotes are indistinguishable phenotypically from wild type mice, they must be identified by a PCR based genotyping assay.
When using the B6-staggerer mouse strain in a publication, please cite the originating article(s) and include JAX stock #002651 in your Materials and Methods section.