A/WySnJ

Stock number: 000647
Product name: A Woolley Snell
Research areas: Cancer Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

A/WySnJ mice are similar to A/J mice (#000646), but carry a spontaneous mutation in Tnfrsf13c and exhibit a significant loss of mature B cells.

Detailed description

The A inbred strain, from which this substrain is derived, is used widely used in cancer and immunology research. It is highly susceptible to induction of congenital cleft palate by cortisone. It has a high incidence of spontaneous lung adenomas and lung tumors readily develop in response to carcinogens. High percentage of mammary adenocarcinomas (a large proportion acinar type) develop in multiparous females. Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed in The Jackson Laboratory substrains.

Unlike A/J mice, A/WySnJ mice carry a spontaneous mutation in Tnfrsf13c and exhibit a significant loss of mature B cells (Miller, et al., 1991, Lentz et al., 1996, Shulga-Morskaya et al., 2004).

Development

In 1921 LC Strong crossed a Bagg albino with a Cold Spring Harbor albino stock, maintained by Little, to begin the A/St strain. In 1927 John Bittner began his subline (A/Bi) and when he left The Jackson Laboratory in 1942 the A/Bi subline was maintained by the laboratory then, subsequent to the 1947 fire, by George Wooley and subsequently transferred to GD Snell in 1951. In 1995 this strain was cryopreserved at generation F227. The substrain branch leading to A/WySnJ has been separated from the original A strain and the branch leading to the A/J substrain since 1927.

Allele

Symbol: Tnfrsf13c^Bcmd1
Name: B-cell maturation defect 1
MGI accession ID: MGI:2389403
Generation method: Spontaneous
Marker symbol: Tnfrsf13c
Marker name: tumor necrosis factor receptor superfamily, member 13c
Chromosome: 15
Strain of origin: A/WySnJ
Molecular note: In the A/WySnJ strain of mice, an intracisternal type A particle retrotransposon insertion occurred in exon 3, resulting in the replacememt of the final 8 amino acids of the encoded protein with 21 amino acids from the inserted element. This mutation is not present in A/J. FACS analysis indicated that an aberrant fusion protein was expressed from this allele that appeared on the cell surface; however, the protein appeared to be nonfuctional.

Allele

Symbol: Il3ra^m1
Name: mutation 1
MGI accession ID: MGI:3652833
Generation method: Spontaneous
Marker symbol: Il3ra
Marker name: interleukin 3 receptor, alpha chain
Chromosome: 14
Strain of origin: multiple strains
Molecular note: Sequence analysis revealed A/J mice lack the sequence corresponding to exon 8, which encodes 10 amino acid residues in the extracellular domain. Aberrant splicing was due to a 5 base pair deletion at the branch point in intron 7.
General note: This allele has been identified in A/J, A/WySnJ, A/HeJ, C58/J, RF/J, AKR/J, SM/J, BUB/BnJ, CE/J, and NZB/B1NJ. see J:24918.

Allele

Symbol: Hc⁰
Name: deficient
MGI accession ID: MGI:3027637
Generation method: Spontaneous
Marker symbol: Hc
Marker name: hemolytic complement
Chromosome: 2
Strain of origin: multiple strains
Molecular note: A 2 base "TA" deletion at positions 62 and 63 of an 83 base pair exon near the 5' end of the gene is found in the following mouse strains: A/HeJ, A/J, AKR/J, DBA/2J, I/LnJ, KK/HlJ, MOLF/EiJ, NZB/B1NJ, RF/J, ST/bJ SWR/J, B10.D2/oSnJ. The consequence of this deletion is the creation of a stop codon starting four bases after the deletion. A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5.
General note:

This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, A/J, AKR/J, DBA/2J, NZB/B1NJ, SWR/J, B10.D2/oSnJ

Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The A/J allele contains a 2 bp deletion resulting in deficient Hc mRNA and protein production and is associated with susceptibility to allergen-induced bronchial hyperresponsiveness. (J:108211)

Allele

Symbol: Wnt9b^clf1
Name: cleft lip 1
MGI accession ID: MGI:1856821
Generation method: Spontaneous
Marker symbol: Wnt9b
Marker name: wingless-type MMTV integration site family, member 9B
Chromosome: 11
Strain of origin: A/WySn
Molecular note: This mutation is a novel insertion of an IAP transposon 3' from the gene. In addition, a standard genetic test of allelism between clf1 and a Wnt9b targeted mutation demonstrated noncomplementation, showing clf1 is an allele of Wnt9b.
General note: Unequal duplicate epistasis - the normal allele at clf1 is a dominant suppressor of the recessive phenotype at clf2, and the normal allele at clf2 is a semidominant suppressor of the recessive phenotype at the clf1 locus.

Allele

Symbol: Cdh23^ahl
Name: age related hearing loss 1
MGI accession ID: MGI:3028349
Generation method: Spontaneous
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Chromosome: 10
Strain of origin: multiple strains
Molecular note: Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G to A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.