B6.Cg-Rora^sg + +/+ Myo5a^d Bmp5^se/J

Stock number: 000285
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, 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.

In this congenic strain the staggerer mutation is maintained in repulsionwith both the dilute (Myo5a^d) and short ear (Bmp5^se) mutations.

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. In 1978, which the line was at generation F55, Myo5a^d Bmp^se was backcrossed onto C57BL/6J seven times through a two generation backcross-intercross breeding scheme; at F58, Rora^sg was backcrossed onto C57BL/6J four times also by backcross-intercross. 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 1982, after 4 or 5 generations of sibling crosses, embryos were generated for cryopreservation from proven Rora^sg + +/+ Myo5a^d Bmp5^se repulsion heterozygous males bred to females that were likely also repulsion heterozygotes. The recovered pups are expected to be either homozygous for Rora^sg and wildtype for dilute and short ear, wildtype for Rora and homozygous for dilute or short ear, or have no phenotype and be repulsion heterozygotes Rora^sg + +/+ Myo5a^d Bmp5^se.

Allele

Symbol: Rora^sg
Name: staggerer
MGI accession ID: MGI:1857035
Generation method: Spontaneous
Synonyms: RORalpha^-; sg
Marker symbol: Rora
Marker name: RAR-related orphan receptor alpha
Marker synonyms: 9530021D13Rik; IDDECA; Nr1f1; ROR1; ROR2; ROR3; RORa1; RORalpha; RZRA; RZR-ALPHA; tmgc26
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: Bmp5^se
Name: short ear
MGI accession ID: MGI:1856150
Generation method: Spontaneous
Synonyms: se^GnJ
Marker symbol: Bmp5
Marker name: bone morphogenetic protein 5
Chromosome: 9
Strain of origin: mice from Abbie Lathrop mouse farm
Molecular note: The C to T substitution creates a stop codon at arginine codon 208 (p.R208*). The resulting truncated protein does not include the carboxy terminal signaling portion of the molecule.
General note: Phenotypic Similarity to Human Syndrome: Ear, Patella, Short Stature Syndrome (Meier-Gorlin Syndrome) in homozygous mice (J:24474)

Allele

Symbol: Myo5a^d
Name: dilute
MGI accession ID: MGI:1856004
Generation method: Spontaneous
Synonyms: blue dilution; d; d^v; Maltese dilution
Marker symbol: Myo5a
Marker name: myosin VA
Marker synonyms: 9630007J19Rik; Dbv; Dop; flail; GS1; MVa; Myh12; MYO5; MyoVA; MYR12; nmf244
Chromosome: 9
Strain of origin: old mutant of the mouse fancy
Molecular note: This mutation is the result of the integration of ecotropic murine leukemia virus Emv-3 into a noncoding region of the Myo5a^d gene. Reversions of Myo5a^d to wild-type are caused by excision of the virus leaving exactly one long terminal repeat in place.