B6.Cg-Kit^W/J

Stock number: 000164
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

Allele

Symbol: Kit^W
Name: dominant spotting
MGI accession ID: MGI:1856232
Generation method: Spontaneous
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
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).