WB/ReJ Kit^W/J

Stock number: 000692
Product name: WB
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

Kit mice possess pleiotropic defects in pigment-forming cells, germ cells, RBC's and mast cells. In addition, they exhibit impaired resistance to parasitic infection and an intrinsic progenitor cell defect. The lack of germ cells in homozygous mutant mice leads to the development of some ovarian tumors (mesotheliomas and granulosa cell), associated with an overproduction of pituitary gonadotropic hormone. Kit mice generally have a well-defined belly spot with sharp edges and a very variable amount of white in the dorsal coat.

Detailed description

Kit mice possess pleiotropic defects in pigment-forming cells, germ cells, RBC's and mast cells. In addition, they exhibit impaired resistance to parasitic infection and an intrinsic progenitor cell defect. The lack of germ cells in homozygous mutant mice leads to the development of some ovarian tumors (mesotheliomas and granulosa cell), associated with an overproduction of pituitary gonadotropic hormone.

Development

Mice carrying the Kit^W mutation were sent from Dr. S. J. Holman and Dr. Salome Waelsch to Elizabeth Russell at The Jackson Laboratory in the late 1940?s. Female #168 was bred with male #169 to begin the generation of inbred lines segregating for Kit^W and the resulting inbred lines were selected for frequency and longevity of homozygotes. The lines were maintained by full sibling inbreeding and line WB separated from WC at generation F8. Prior to F25 homozygotes on the WB background showed an average lifespan of 10.6 days. Additionally, the mean age of first litter at that time, 75 days, was earlier than that of WC, which was 92 days of age (Russell and McFarland, 1966). In 1960 WB/Re reached generation F36, in 1965 F56, in 1975 F97, in 1986 F126, in 1992 F138, and in 2010 F191. Embryos were cryopreserved in 1987.

Allele

Symbol: Pde6b^rd1
Name: retinal degeneration 1
MGI accession ID: MGI:1856373
Generation method: Spontaneous
Synonyms: Pdeb^rd1; rd; rd1; rd-1; rodless retina
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Marker synonyms: CSNB3; CSNBAD2; GMP-PDEbeta; nmf137; PDEB; r; rd; rd1; rd10; RP40
Chromosome: 5
Strain of origin: various
Molecular note: Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C-to-A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain, has been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.
General note: The following inbred strains are known to be homozygous for Pde6b: C3H sublines, CBA/J, FVB/NJ, PL/J, SB, SJL/J, and SWR/J.

Allele

Symbol: Kit^W
Name: dominant spotting
MGI accession ID: MGI:1856232
Generation method: Spontaneous
Synonyms: W
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Marker synonyms: belly-spot; CD117; c-KIT; Dominant white spotting; Gsfsco1; Gsfsco5; Gsfsow3; MASTC; PBT; SCFR; SCO1; SCO5; SOW3; Steel Factor Receptor; Tr-kit
Chromosome: 5
Strain of origin: old mutant of the mouse fancy
Molecular note: A G-to-A substitution at the first nucleotide at the 5' boundary of intron 10 following the transmembrane exon 10 results in two different aberrantly spliced transcripts putatively expressed in a tissue specific manner. A deletion of 107 bp was found in transcripts from mast cells of mutant mice. A deletion of 234 bp was found in transcripts from brain or bone marrow cells. The mutation disrupts splice donotr site G-GT by changing it to G-AT point, thereby causing exon skipping. The 107 bp deletion could have resulted from skipping of a transmembrane region exon and the 234 bp deletion from skipping 3 exons. The 107 bp deletion would create a frame shift with a stop codon 12 bp downstream, whereas the larger deletion would still be in frame. Northern blot analysis indicated that mast cells from mutants have only 31-37% of the transcripts as mast cells derived from normal bone marrow, suggesting that the mutation may reduce efficiency and authenticity of transcription and splicing.
General note: This is an old mutant of the mouse fancy. Kit^W mutants are a potential model for human inherited pure red cell anemia, called Diamond-Blackfan anemia (OMIM 205900), but mouse mutants do not respond to corticosteroid treatment as do human patients. Thus, the mechanism of anemia causation in the two conditions must be different (J:14286).