B6C3Fe a/a-Glrb^spa/J

Stock number: 000241
Product name: spastic
Research areas: Cell Biology Research, Neurobiology Research

Detailed description

Mice homozygous for the spastic spontaneous mutation (Glrb^spa) can usually be recognized at 14 days of age, but some mutant mice may not be reliably distinguished until 5 or 6 weeks of age. They show spastic symptoms in response to handling, but spastic behavior can occur spontaneously. The spasms consist of rapid tremor, stiffness of posture, and difficulty in righting when placed on the back. No anatomical pathology occurs in either muscle or the central nervous system, except that herniated intervertebral discs and cysts of the leptomeninges occur, most severely in the lumbar region, possibly resulting from traumatic injuries sustained during the myoclonic episodes. The spastic symptoms can be markedly alleviated by intraperitoneal injection of aminooxyacetic acid, an inhibitor of g-aminobutyric acid transaminase (GABA-T), but not by Dilantin or trimethadione. Glycine receptor expression in the CNS of spastic mice is reduced to 20%, or less, of normal.

Development

The spastic mutation (spa) arose spontaneously in the early 1960's at The Jackson Laboratory in a hybrid stock belonging to C. F. Chai that was produced by intercrosses of 6 inbred strains: C57BL/6J, C57BR/cd, A/J, BALB/c, LG and SM. This B6C3Fe-a/a stock of spastic was begun in 1973 by mating a B6.Cg-spa homozygous female at generation N5F5 to a C3H/Gn-a/a male and intercrossing the offspring. A homozygous female from the intercross was then crossed to a B6C3Fe-a/a F1 male and this stock was maintained through this cross-intercross using B6C3Fe-a/a F1 for the cross. In 1997 embryos were generated for cryopreservation by mating heterozygotes at generation N47.

Allele

Symbol: Glrb^spa
Name: spastic
MGI accession ID: MGI:1856363
Generation method: Spontaneous
Synonyms: spa
Marker symbol: Glrb
Marker name: glycine receptor, beta subunit
Marker synonyms: HKPX2
Chromosome: 3
Strain of origin: Not Specified
Molecular note: The mutation in the spastic mouse is an insertion of a 7.1 kilobase LINE-1 element within intron 6 of the gene. Glrb mRNA is markedly reduced throughout brains of homozygous mice, and was shown to be aberrantly spliced.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
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