Strain Name: |
B6CBACa Aw-J/A-Kcnj6wv/J |
|---|---|
Stock Number: |
000247 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
B6CBACa-Aw-J/A-Kcnj6wv (Changed: 15-DEC-04
) |
| Genes & Alleles | Aw-J; Kcnj6; Kcnj6wv; a; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Mutant Strain Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Spontaneous Mutation Species laboratory mouse Generation N31 Appearance
white-bellied agouti, ataxic
Related Genotype: Aw-J/? Kcnj6wv/Kncj6wv
agouti, ataxic
Related Genotype: A/A Kcnj6wv/Kncj6wv
white-bellied agouti, unaffected
Related Genotype: Aw-J/? +/? or Aw-J/A Kncj6wv/+
agouti, unaffected
Related Genotype: A/A +/? or A/A Kncj6wv/+Strain Description
Mice homozygous for the weaver spontaneous mutation (Kcnj6wv) 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 Kcnj6wv/Kcnj6wv and Kcnj6wv/+ 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 Kcnj6wv acts non-autonomously and encodes a membrane-associated ligand that induces external germinal layer neuron differentiation.Strain Development
Weaver (Kcnj6wv) 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.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Aw-J | ||
|---|---|---|---|
| Allele Name | white bellied agouti Jackson | ||
| Common Name(s) | AWJ; | ||
| Strain of Origin | C57BL/6J | ||
| Gene Symbol and Name | a, nonagouti | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | AGSW; AGTI; AGTIL; ASP; As; MGC126092; MGC126093; SHEP9; agouti; agouti signal protein; agouti suppressor; | ||
| Allele Symbol | Kcnj6wv | ||
| Allele Name | weaver | ||
| Common Name(s) | wv; | ||
| Strain of Origin | C57BL/6J | ||
| Gene Symbol and Name | Kcnj6, potassium inwardly-rectifying channel, subfamily J, member 6 | ||
| Chromosome | 16 | ||
| Gene Common Name(s) | BIR1; GIRK2; KATP2; KCNJ7; KIR3.2; MGC126596; hiGIRK2; weaver; wv; | ||
| General Note | Homozygotes are recognizable in the second postnatal week by small size, instability of gait, weakness, and hypotonia. Many die at weaning age, but some survive to adulthood and females may breed (J:30520). Adult weaver mice, both homozygotes and heterozygotes, are also subject to sudden unexplained death (Sweet HO, 1995, personal communication).The cerebellum of weaver mutants is very small and simple and almost devoid of granule cells, which degenerate during the second week of life (J:30520). Although it has been suggested that granule cell death is due to failure of migration, more recent studies suggest that an earlier event causes cell death (J:16025). Purkinje cells are somewhat disarranged and have small dendritic trees (J:30722). By electron microscopy, the Purkinje cells are seen to have normal dendritic spines with normal postsynaptic terminals, but their presynaptic mates from the parallel fibers of the granule cells are missing (J:5315). Purkinje cells of cerebellar origin are reduced in number but those remaining have the same density of GABAergic terminals as in normal mice (J:2651). Kcnj6wv/+ heterozygotes show normal behavior, but have a smaller than normal cerebellum with a deficiency of granule cells, some of which have not migrated into the internal granule layer and remain scattered in the molecular layer (J:5294). The defect in Kcnj6wv/Kcnj6wv and Kcnj6wv/+ mice first becomes apparent at about 5 days of age and consists of a reduced rate of migration of granule cells into the internal granule layer, the defect being more severe in homozygotes than in heterozygotes. Granule cells migrate inward along radially distributed Bergmann glial fibers (J:5294). Cytological abnormalities are found in some Bergmann fibers in homozygotes, indicating that the basic defect caused by the mutation might lie in these fibers (J:5394). Later evidence from cultures of mutant and wild type cerebellum showed that granule cells of heterozygous and homozygous weaver mice have gene-dosage dependent abnormalities of morphology and cell behavior (J:15542, J:6671). In wild type/weaver chimeras with cellular markers for granule cells and Purkinje cells, the migration defect of granule cells is intrinsic to the granule cells themselves. The disarrangement of Purkinje cells is not caused by intrinsic action of Kcnj6wv in these cells (J:6865). Cell mixing experiments also suggest that the mutation acts non-autonomously and encodes a membrane-associated ligand that induces external germinal layer neuron differentiation (J:2009). Several secondary effects of the weaver defect on other cell types and their interconnections in the cerebellum have been described (J:5745, J:5395, J:5556). The weaver mutant has been suggested as a model for Parkinsonism (OMIM 168600) (J:29229). The loss of dopaminergic cells of the substantia nigra in weaver mice (J:30520) parallels loss of the same cell type in Parkinsonism. However, Bandmann et al. (J:33925) failed to find abnormalities of sequence in the human homolog of Kcnj6 in Parkinson patients (J:33925). Although the morphology of the cerebrum appears unaffected by Kcnj6wv, parts of the cerebrum of homozygotes show a marked deficiency of dopamine, particularly in the frontal cortex and the dorsal striatum, with a smaller deficiency in the olfactory tubercle, and normal levels in the ventral striatum (J:944, J:7280, J:6717). Tyrosine hydroxylase activity is also lower than normal and dopamine uptake activity is reduced (J:14336, J:974, J:922). Choline and GABA uptake appear unaffected (J:922). Regions of dopamine deficiency exhibit elevated serotonin content (J:922), probably due to a higher density of serotonin-immunoreactive fibers (J:805). The homozygous weaver mutant has been used to show that there is insignificant somatodendritic uptake of dopamine in the substantia nigra (J:12653). The density of some, but not all, opioid receptors is reduced in homozygous mutants (J:1708). A reduction in amyloid beta-protein precursor (betaAPP) in the cerebellum and substantia nigra appears to be secondary to nerve cell loss (J:4115). Ion selectivity of the Kcnj6 IRK is altered in weaver mice, giving rise to inward Na+ currents (J:31621). IRK K+ currents are lost in cerebellar granule cells (J:35792). The sterility of Kcnj6wv/Kcnj6wv males is due to a lack of sperm. Sperm fail to mature, and both spermatogenic cells and supporting cells of the seminiferous epithelium degenerate (J:18348, J:16319). Heterozygotes also show degenerative effects, but less severely and at a later age. It has been suggested that degeneration of spermatocytes and immature sperm may be secondary to Sertoli cell degeneration (J:23163). | ||
| Molecular Note | A G-to-A transition at position 953 replaces a Gly with Ser at amino acid residue 156, affecting the highly conserved H5 domain of the channel. [MGI Ref ID J:29230] [MGI Ref ID J:30864] | ||
Control Information
| Allele | Control | |
|---|---|---|
| Kcnj6wv | Untyped from the colony | |
| Considerations for Choosing Controls | ||
Genotyping Protocols
Aw-J
Related Strains
Strains carrying Aw-J allele
View Strains carrying Aw-J (31 strains)
004200 B6;CBACa Aw-J/A-Npr2cn-2J/J
Research Applications
This mouse can be used to support research in many areas including:Kcnj6wv related
Cell Biology Research
Channel and Transporter Defects (potassium)
Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Channel and Transporter Defects (potassium)
Epilepsy
References
Selected Reference(s)
Additional ReferencesHirano A; Dembitzer HM. 1973. Cerebellar alterations in the weaver mouse. J Cell Biol 56(2):478-86. [PubMed: 4118891] [MGI Ref ID J:5315]
Yao W; Zhong J; Rosen CJ; Hock JM; Lee WH. 2005. Igf-I and postnatal growth of weaver mutant mice. Endocrine 26(2):117-25. [PubMed: 15888923] [MGI Ref ID J:109832]
Price and Supply Information
| Strain Name: | B6CBACa Aw-J/A-Kcnj6wv/J |
| Stock Number: | 000247 |
Price Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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