JAX Notes January 01, 1991

The coat colors of mice with macrocytic anemia

Gene description

The Jackson Laboratory produces both the WBB6F1/J-W/Wv (WBB6F1/J-KitW/KitW-v/J – 100410) and WCB6F1/J-Sl/Sld mice. [Note:  The latter strain, WCB6F1/J-KitlSl/KitlSl-d/J  (100401)  was discontinued in 2013.  The two parental strains that were crossed to make this F1 - WC/ReJ KitlSl/J (000693) and B6.D2-KitlSl-d/J (000160)  - remain available.] These mice have a severe macrocytic, normochromic anemia. The W/Wv mice, because they have a heritable hematopoietic progenitor cell defect, accept, without prior total body irradiation, stem cell transfers from C57BL/6J or WBB6F1/J-+/+ mice. The Sl/Sld mice, because they have a defective hematopoietic microenvironment, do not accept stem cell transfers.

It has been shown that the W locus codes for Kit, a receptor protein kinase, and Sl encodes the W ligand. Not only do both these genes affect blood cell formation, but they also affect the coat color of the mouse, causing reduced pigmentation or variable white spotting or both, and germ cell migration, leading to sterility in double heterozygotes. The mice maintained by JAX include: dominant spotting (W); viable dominant spotting (Wv); steel (Sl); steel-Dickie (Sld). The coat color variation is further affected by combinations of the anemic mutant genes and the associated genetic background.

Mating schemes

The following photographs and legends are intended to aid the investigator who is using anemic mice for the first time in identifying the various phenotypes. The pictures on page 3 depict all of the mice in the sequence of matings that lead to WBB6F1/J-W/Wv anemic mice. Specifically, WB/ReJ-W/+ and WB/ReJ-+/+ littermates are mated to produce more WB/ReJ-W/+ mice, one of the components of the F1 hybrids. Similarly, C57BL/6J-Wv/+ and C57BL/6J-+/+ littermates are mated to produce the other hybrid component, C57BL/6J-Wv/+. The WB/ReJ-W/+ and C57BL/6J-Wv/+ mice are then crossed to produce the desired WBB6F1-W/Wv along with WBB6F1/J-Wv/+, WBB6F1/J-W/+, and WBB6F1/J-+/+. Page 4 a parallel sequence of photographs for Sl and Sld.

Photo legends

The legends do not exactly match all of the photographs. The legends include nearly all coat color variations that you may encounter, although some may occur very infrequently. For example, WB/ReJ-W/+ mice have an occasional head blaze, but more often they do not. Also, in the photographs there is little or no difference discernible between the dorsal view of dark gray and black mice, C57BL/6J-Wv/+ and C57BL/6J-+/+ for instance. When observing the mice directly, however, this difference is apparent.

References

Anderson DM, Lyman SD, Baird A, Wignall JM, Eisenman J, Rauch C, March CJ, Boswell HS, Simpel SD, Cosman D, Williams DE. Molecular cloning of mast cell growth factor, a hematopopietin that is active in both membrane bound and soluble forms. Cell 1990; 63:235-243.

Copeland NG, Gilbert DJ, Cho BC, Donovan PJ, Jenkins NA, Cosman D, Anderson D, Lyman SD, Williams DE. Mast cell growth factor maps near the steel locus on mouse Chromosome 10 and is deleted in a number of steel alleles. Cell 1990; 63; 175-183.

Flanagan JG, Leder P. The kit ligand. A cell surface molecular altered in steel mutant fibroblasts. Cell 1990;63:185-194.

Huang E, Nocka K, Beier DR, Chu T-Y, Buck J, Lahm H-W, Wellner D, Leder P, Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990; 63-225-233.

Pawson T, Bernstein A. Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends in Genet 1990; 71:350-356.

Russell ES. Hereditary anemias of the mouse; a review for geneticists. Adv Genet 1979; 20:357-459.Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hau R-Y, Birkett NC, Okino KH, Murdock DC, Jacobsen FW, Langley KE, Smith KA, Takeishi T, Cattanach BM, Galli SJ, Suggs SV. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990; 63:213-224.