B6.Cg-T^2J +/+ Qki^qk-v/J

Stock number: 000567
Product name: quaking viable/brachyury 2 Jackson

Research areas: Apoptosis Research, Cell Biology Research, Developmental Biology Research, Neurobiology Research, Reproductive Biology Research, Sensorineural Research

Description

These mice carry two spontaneous mutations, brachyury 2 Jackson (T^2J) and quaking viable (Qki^qk-v) in repulsion. Brachyury 2 Jackson mice are characterized by short tails and tremors, and quaking viable mice by tremors and myelin deficiency.

Detailed description

Mice homozygous for the quaking viable spontaneous mutation (Qki^qk-v) have marked rapid tremor which disappears when they are at rest but increases during locomotion. The tremor in homozygous mutant mice begins at about 10 days and is fully developed by 3 weeks. Mature mice may have seizures in which a motionless posture is maintained for many seconds. Females are viable and fertile, males are sterile due to defective spermatic differentiation. The entire CNS of quaking mutant mice is severely deficient in myelin and there is a less severe myelin deficiency in the PNS. In this strain the brachyury 2 Jackson mutation (T^2J), which causes shortened tails in heterozygotes, is maintained in repulsion with the quaking viable mutation as an outwardly evident indicator of genotype.

Development

The quaking (qk-v) mutation, also called quaking viable, arose spontaneously in 1961 in the DBA/2J strain. It was crossed twice to C3H then transferred to the C57BL/6JEi background via backcross-intercross mating until N10 then sibling bred. At N11F10 it was bred to C57BL/6J-T^2J, and a repulsion stock was generated. In 1994 T^2J +/+ Qki^qk-v females were bred with T^2J +/+ Qki^qk-v males, all at or beyond N18F19, to generate embryos for cryopreservation.

Allele

Symbol: Qki^qk-v
Name: quaking viable
MGI accession ID: MGI:1856539
Generation method: Spontaneous
Synonyms: qk; Qk^qk; qk^v
Marker symbol: Qki
Marker name: quaking, KH domain containing RNA binding
Marker synonyms: 1110003F05Rik; Hqk; hqkI; l(17)-1Wis; l17Wis1; Qk; QK1; QK3; QkI
Chromosome: 17
Strain of origin: DBA/2J
Molecular note: The quaking phenotype has been attributed to a 1.85 Mb deletion on chromosome 17. The proximal breakpoint was located in the promoter region of the Qk gene and affects transcript levels of that gene. The distal breakpoint lies between exons 5 and 6 of the parkin gene. Both the parkin gene and another co-regulated gene, Pacrg, are inactivated. Although parkin is not expressed in these mutants, the described phenotype appears due to to the defect in Qk expression.
General note: The quaking mutation arose spontaneously in the DBA/2J strain. Homozygotes have marked rapid tremor which disappears when they are at rest but increases during locomotion. It begins at about 10 days and is fully developed by 3 weeks. Mature mice may have seizures in which a motionless posture is maintained for many seconds. Females are viable and fertile, males sterile. Homozygotes are severely deficient in myelin, the material which ensheathes and insulates the axons of the central (CNS) and peripheral (PNS) nervous systems (see Mbp). The entire CNS is very deficient in myelin at all ages (J:13141), and there is a less severe myelin deficiency in the PNS nervous system (J:5177). Myelin sheaths are present in the CNS, but they are thinner than normal, some consisting of only one to four myelin lamellae. The sheaths are usually loosely wound, with patches of oligodendroglial cell cytoplasm between the lamellae, and there are abnormal inclusions and vacuoles in the processes and perikarya of oligodendrocytes. Development of the myelin sheaths appears to be arrested in a stage characteristic of very young animals (J:5189)(J:5271)(J:5218). There is variable hyperplasia of oligodendrocytes, greatest in the tracts with the greatest degree of myelination (J:5615). Axons have normal morphology but there is abnormally high proteolysis in the axons of the optic nerve (J:6971). There is evidence that the myelination defect in the CNS is due to defective oligodendrocytes (J:6216). Handling-induced convulsive seizures in qk/qk mice can be inhibited by administration of N-methyl-D-aspartate (NMDA) antagonists. Modulatory mechanisms for the NMDA receptor complex may differ in qk/qk mice from wild-type (J:1930). a2-adrenoceptor (A2A) antagonists also inhibit these seizures, while A2A agonists potentiate them. qk/qk mice have increased brain binding sites for A2A agonists (J:1169). In the PNS, thinly myelinated and unmyelinated fibers have been described in the sciatic nerve and in the intracranial portion of the trigeminal nerve (J:5189)(J:5271). The sheaths may be structurally abnormal with regions of uncompacted myelin lamellae similar to those of the CNS (J:5778). Orthotopic transplantation of pieces of sciatic nerve between quaking and normal mice has shown that the genetic defect is expressed in Schwann cells (J:14892). Qk causes defective myelinogenesis in both oligodendrocytes and Schwann cells (J:6411). There is an extensive literature on biochemical defects related to the deficiency of myelin in quaking mice (J:26986), a consistent finding of which is a severe deficiency of the myelin lipids, sphingomyelin, cerebrosides, and sulfatides, particularly those containing long-chain fatty acids. The normal increase in these fatty acids which occurs between 15 and 20 days does not occur in qk/qk mice, so that adult mutants tend to resemble very young controls (J:5171). Brain proteolipids in adult quaking mice retain the relative proportions found in 10-day controls (J:5408). The myelin-associated glycoproteins of different molecular weight in the brains of quaking mice 15 days of age and older are expressed in abnormal proportions (J:7990). Synthesis of myelin basic protein and proteolipids is normal in quaking brains but their incorporation into myelin is defective (J:6151). mRNAs for myelin basic protein, for example, occur in oligodendrocyte cell bodies, but not in the cell processes that actually form the myelin sheath, in qk/qk brain (J:1931). Quaking mice may have abnormal levels of copper and zinc in the brain, but the evidence on this point is conflicting (J:7214). The sterility of male qk/qk mice is due to defective spermatid differentiation, the details of which have been described (J:5241). It has been further demonstrated that male sterility in these mice is the result of the loss of Pacrg expression (J:90667).

Allele

Symbol: T^2J
Name: brachyury 2 Jackson
MGI accession ID: MGI:1856190
Generation method: Spontaneous
Marker symbol: T
Marker name: brachyury, T-box transcription factor T
Marker synonyms: Bra; SAVA; T1; Tbxt; TFT
Chromosome: 17
Strain of origin: C57BL/6J
Molecular note: Pulsed-field gel electrophoresis revealed an altered restriction fragment size consistent with a deletion of 80-110kb.