Table 2 MC-deficient animal models and their characteristics31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46
From: Advances in mast cell biology: new understanding of heterogeneity and function
Species | Genotype | Mutation | Characteristics |
|---|---|---|---|
Mouse | W/W v | CD117 (c-kit) is encoded at white spotting (W) locus on mouse chromosome 5 Heterozygous with point mutation that causes exon skipping and produces truncated CD117 (W mutation), and point mutation in the tyrosine kinase domain of CD117 (Wv, W-viable mutation) | White coat color due to lack of melanocytes Sterile due to lack of germ cells Anemic, develop stomach papillomas and ulcers, and idiopathic dermatitis Decrease in the number of bone marrow and blood neutrophils Lack of interstitial cells of Cajal and TCRγδ T cells in small intestine <1% of MC number of wild type Restoring MCs after transfer of BMMCs |
Sl/Sl d | SCF is encoded at steel (Sl) locus on mouse chromosome 10 Heterozygous that have ∼973 kb deletion of Sl locus including all SCF coding region (Sl mutation) and 4 kb intragenic deletion of SCF coding region that retains expression of soluble but not transmembrane SCF (Sld, Steel-Dickie mutation) | White coat color due to lack of melanocytes Sterile due to lack of germ cells Anemic Lack of interstitial cells of Cajal <1% of MC number of wild type Restoring MCs after injection of SCF | |
W sh /W sh | Inversion of a segment of chromosome 5, ∼70 kb upstream of the CD117 gene (Wsh, W-sash mutation) This inversion disturbs regulatory elements and markedly reduces CD117 expression | White sash coat around their midsection Fertility, lack of anemia, and availability in a uniform C57BL/6 background into which they have been backcrossed More severe MC deficiency than W/WV mice Restoring MCs after transfer of BMMCs | |
mi/mi | mi locus on chromosome 6 of mice encodes MITF. MITF is basic-helix-loop-helix leucine zipper type of transcription factor and mi mutation leads to lacking 1 of the 4 consecutive arginine residues in the basic domain that abolishes DNA binding ability of MITF Because CD117 expression is regulated by MITF, mi/mi mouse have MC deficiency | Depletion of pigment in hair and eyes Microphthalmia Osteopetrosis due to lack of osteoclasts ∼35% of MC number of wild type Downregulation of gene expression regulated by MITF (CD117, MMCP-1, -2, -4, -5, -6, -7, -9, tryptase, granzyme B, NDST-2, tryptophan hydrolase, p75 NGFR, melanocyte-stimulating hormone receptor, SglGSF) Restoring MCs after transfer of BMMCs | |
Rat | Ws/Ws | Homozygous that have deletion of 12 bases (four amino acids) located two amino acids downstream from tyrosine autophosphorylation site of CD117 (Ws, White Spotting mutation) | Black-eyed white coat color Anemic due to lack of erythrocytes <1% of MC number of wild type Lack of FcɛRI β-subunit expression Restoring MCs after transfer of BMMCs |
