B6CBACa A^w-J/A-Kcnj6^wv/J

Stock number: 000247
Product name: weaver
Research areas: Cell Biology Research, Neurobiology Research

Detailed description

Mice homozygous for the weaver spontaneous mutation (Kcnj6^wv) are recognizable in the second postnatal week by their small size, instability of gait, weakness, and hypotonia. Many homozygous mutant mice die at weaning age, but some survive to adulthood, and females may breed. The cerebellum in homozygous mutants is very small, simple, and almost devoid of granule cells, which degenerate during the second week. Heterozygotes behave normally, but they have a smaller than normal cerebellum with a deficiency of granule cells, some of which fail to migrate into the internal granule layer and remain scattered in the molecular layer. Evidence from cultures of mutant and normal cerebellum show that granule cells of Kcnj6^wv/Kcnj6^wv and Kcnj6^wv/+ mice have gene-dosage dependent abnormalities in morphology and cell behavior. Studies using homozygous weaver/wildtype chimeras indicate that the migration defect of granule cells is intrinsic to the granule cells themselves. The disarrangement of Purkinje cells, however, is not caused by intrinsic action of weaver in these cells. Cell mixing experiments also suggest Kcnj6^wv acts non-autonomously and encodes a membrane-associated ligand that induces external germinal layer neuron differentiation.

Development

Weaver (Kcnj6^wv) arose spontaneously in the pedigreed expansion stocks of C57BL/6J at The Jackson Laboratory in 1961. It was maintained by mating tested pairs until F21. Ovarian transplantation to C57BL/6J was used to F21N3 and then because of poor breeding performance a weaver (wv/wv) male was outcrossed to a CBA/Ca female and the tested offspring (wv/+) were mated to the B6CBACa hybrids. Backcrossing to the hybrid B6CBACa was then made each generation by mating a homozygous female weaver to a hybrid and mating the known heterozygotes. The stock was at N46 in 1992. It was cryopreserved in 1986 by mating heterozygous females to heterozygous males at N30-N32 or by mating homozygous females to B6CBACa F1 males.

Allele

Symbol: Kcnj6^wv
Name: weaver
MGI accession ID: MGI:1856525
Generation method: Spontaneous
Marker symbol: Kcnj6
Marker name: potassium inwardly-rectifying channel, subfamily J, member 6
Chromosome: 16
Strain of origin: C57BL/6J
Molecular note: A G-to-A transition at coding nucleotide 466 replaces a glycine with serine at amino acid residue 156 (p.G156S), affecting the highly conserved H5 domain of the channel.

Allele

Symbol: A^w-J
Name: white bellied agouti Jackson
MGI accession ID: MGI:1855946
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Chromosome: 2
Strain of origin: C57BL/6J