Related Experiment Video
Updated: May 20, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
A novel Kit gene mutation in CF1 mice involved in the extracellular domain of the KIT protein
Shuji Takabayashi1, Tetsu Nishikawa, Hideki Katoh
1Institute for Experimental Animals, Hamamatsu University School of Medicine, 1–20–1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Abstract:
We screened for natural mutations in Crl:CF1 closed colony mice using an ordinary backcrossing system. Five of 30 CF1 males carried novel genes that caused white spots on colored coats. Their backcross progenies showed a white spot phenotype. The white spot gene was mapped to approximately 39 cM on chromosome 5, where the Kit gene is known to reside. Allelism testing between this spot gene and the Kit gene was performed using two already known Kit alleles, Kit(W), and Kit(W-v). We demonstrated that the spot mutation was semidominant and a novel allele of the Kit gene, which was tentatively named Kit(W-Ham). No infertility or anemia was observed in Kit(W-Ham) homozygotes. However, a reduced number of germ cells and mast cells was observed in Kit(W-Ham)/Kit(W) and Kit(W-Ham)/Kit(W-v) transheterozygotes. Sequencing of the 21 exons of the Kit gene in the Kit(W-Ham) mutants revealed that a unique guanine-to-adenine (G-A) transition at nucleotide position 545 (c.545G>A) of exon 3 changes arginine (R) to glutamine (Q) at position 182 in the extracellular domain of the KIT protein (p.R182Q). This extracellular KIT domain is a binding site for stem cell factors (SCF). It was concluded that the Kit(W-Ham) mutant may serve as a new model of human piebaldism.
Insights
Researchers identified a novel mouse mutation, Kit(W-Ham), causing white spots on colored coats. This mutation, affecting the Kit gene, may serve as a new model for human piebaldism.
Area of Science:
- Genetics
- Developmental Biology
- Mammalian Genetics
Background:
- Natural mutations in mouse coat color genes provide valuable insights into developmental processes.
- The Kit gene is crucial for melanocyte development and is a known target for coat color mutations.
Purpose of the Study:
- To identify and characterize novel spontaneous mutations affecting coat color in mice.
- To investigate the genetic basis of a newly observed white spotting phenotype.
- To determine if the identified mutation is an allele of the known Kit gene.
Main Methods:
- Screening of Crl:CF1 mice for natural coat color mutations using a backcrossing system.
- Genetic mapping of the white spot locus to chromosome 5.
- Allelism testing with known Kit gene alleles (Kit(W) and Kit(W-v)).
- Phenotypic analysis of homozygotes and transheterozygotes for the novel allele.
- DNA sequencing of the Kit gene to identify the causative mutation.
Main Results:
- A novel semidominant mutation, Kit(W-Ham), causing white spotting was identified in five of 30 CF1 males.
- The mutation was mapped to chromosome 5, near the Kit gene locus.
- Allelism testing confirmed Kit(W-Ham) as a novel allele of the Kit gene.
- Kit(W-Ham) homozygotes showed no anemia or infertility, but transheterozygotes exhibited reduced germ and mast cells.
- A specific G-A transition in exon 3 (c.545G>A) resulted in an amino acid change (p.R182Q) in the KIT extracellular domain.
Conclusions:
- The identified mutation, Kit(W-Ham), is a novel allele of the mouse Kit gene.
- The Kit(W-Ham) mutant mouse exhibits a phenotype relevant to human piebaldism.
- This mutant mouse provides a new potential model for studying human piebaldism and the role of the Kit gene in development.
Related Concept Videos
01:16In-vitro Mutagenesis
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...