B6C3Fe a/a-Rora^sg/J

Stock number: 000237
Product name: staggerer
Research areas: Neurobiology Research

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.

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^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. In late 1978, at generation F53, a repulsion heterozygote, (Rora^sg + +/+ Myo5a^d Bmp5^se) was outcrossed to a C3FeLe.B6-a/J and two of their Rora^sg heterozygous offspring, which lacked Myo5a^d and Bmp5^se, were intercrossed to generate a homozygous female from which ovaries were transplanted and the host was bred to a B6C3FeF1/J-a/a male. This line was maintained for many years through this 2-generation breeding scheme, with a homozygous ovarian transplant host being bred to a B6C3FeF1/J-a/a male and then intercrossing their obligate Rora^sg heterozygous offspring. In 2003 embryos were generated for cryopreservation from B6C3FeF1/J-a/a females bred to heterozygous males then at generation NE44F1, having been through 44 two-generation breeding cycles of crossing to the F1 hybrid.

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.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
Molecular note: Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039