ANALYSIS OF PLEIOTROPISM AT THE DOMINANT WHITE-SPOTTING (W) LOCUS OF THE HOUSE MOUSE: A DESCRIPTION OF TEN NEW W ALLELES

1 The Jackson Laboratory, Bar Harbor, Maine 04609

Characterization of the pleiotropic effects of ten new putative W locus mutations, nine co-isogenic and one highly congenic with the C57BL/6J strain, reveals a wide variety of influences upon pigmentation, blood formation and gametogenesis. None of the putative alleles, each of which is closely linked to Ph, a gene 0.1 cM from W, gave evidence of complementation with W39, a new allele previously shown to be allelic to Wv. All W*/W39 genotypes resulted in black-eyed-white anemics with reduced gametogenic activity.1 Homozygotes for seven of these mutations are lethal during perinatal life; anemic embryos have been identified in litters produced by intercross matings involving each of these alleles.—Phenotypes of mice of several mutant genotypes provide exceptions to the frequent observation that a double dose of dominant W alleles (e.g., W/Wv or W/W) results in defects of corresponding severity in each of the three affected tissues. One viable homozygote has little or no defect in blood formation, and another appears to have normal fertility. The phenotypes of these homozygotes support the conclusion that the three tissue defects are not dependent on each other for their appearance and probably do not result from a single physiological disturbance during the development of the embryo.—Although homozygosity for members of this series results in a wide range of phenotypes, the absence of complementation of any allele with W39, the close proximity of each mutant to Ph, and the fact that all alleles produce detectable (though sometimes marginal) defects in the same tissues affected by W and Wv, support the hypothesis that each new mutant gene is a W allele.

Submitted on July 14, 1980
Revised on December 12, 1980




This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
D. Kent, M. Copley, C. Benz, B. Dykstra, M. Bowie, and C. Eaves
Regulation of Hematopoietic Stem Cells by the Steel Factor/KIT Signaling Pathway
Clin. Cancer Res., April 1, 2008; 14(7): 1926 - 1930.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. A. Thoren, K. Liuba, D. Bryder, J. M. Nygren, C. T. Jensen, H. Qian, J. Antonchuk, and S.-E. W. Jacobsen
Kit Regulates Maintenance of Quiescent Hematopoietic Stem Cells
J. Immunol., February 15, 2008; 180(4): 2045 - 2053.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
M. I. Kotlikoff
From genotype to phenotype and back
J. Physiol., January 1, 2007; 578(1): 7 - 8.
[Full Text] [PDF]


Home page
J. Cell Sci.Home page
A. Bashamboo, A. H. Taylor, K. Samuel, J.-J. Panthier, A. D. Whetton, and L. M. Forrester
The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway
J. Cell Sci., August 1, 2006; 119(15): 3039 - 3046.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
M. A. Grimbaldeston, C.-C. Chen, A. M. Piliponsky, M. Tsai, S.-Y. Tam, and S. J. Galli
Mast Cell-Deficient W-sash c-kit Mutant KitW-sh/W-sh Mice as a Model for Investigating Mast Cell Biology in Vivo
Am. J. Pathol., September 1, 2005; 167(3): 835 - 848.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
H.-B. Ruan, N. Zhang, and X. Gao
Identification of a Novel Point Mutation of Mouse Proto-Oncogene c-kit Through N-Ethyl-N-nitrosourea Mutagenesis
Genetics, February 1, 2005; 169(2): 819 - 831.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
H. Ohta, A. Tohda, and Y. Nishimune
Proliferation and Differentiation of Spermatogonial Stem Cells in the W/Wv Mutant Mouse Testis
Biol Reprod, December 1, 2003; 69(6): 1815 - 1821.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Kolbus, M. Blazquez-Domingo, S. Carotta, W. Bakker, S. Luedemann, M. von Lindern, P. Steinlein, and H. Beug
Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling
Blood, November 1, 2003; 102(9): 3136 - 3146.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
F. Guerif, V. Cadoret, V. Rahal-Perola, J. Lansac, F. Bernex, J. Jacques Panthier, M. Therese Hochereau-de Reviers, and D. Royere
Apoptosis, Onset and Maintenance of Spermatogenesis: Evidence for the Involvement of Kit in Kit-Haplodeficient Mice
Biol Reprod, July 1, 2002; 67(1): 70 - 79.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. M. Luger, S. G. O'Brien, J. Ratajczak, M. Z. Ratajczak, R. Mick, E. A. Stadtmauer, P. C. Nowell, J. M. Goldman, and A. M. Gewirtz
Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study
Blood, February 15, 2002; 99(4): 1150 - 1158.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
Y. Ikuno, F.-L. Leong, and A. Kazlauskas
Attenuation of Experimental Proliferative Vitreoretinopathy by Inhibiting the Platelet-Derived Growth Factor Receptor
Invest. Ophthalmol. Vis. Sci., September 1, 2000; 41(10): 3107 - 3116.
[Abstract] [Full Text]


Home page
BloodHome page
G. Berrozpe, I. Timokhina, S. Yukl, Y. Tajima, M. Ono, A. D. Zelenetz, and P. Besmer
The Wsh, W57, and Ph Kit Expression Mutations Define Tissue-Specific Control Elements Located Between -23 and -154 kb Upstream of Kit
Blood, October 15, 1999; 94(8): 2658 - 2666.
[Abstract] [Full Text] [PDF]


Home page
Mol Hum ReprodHome page
M. Mitsunari, T. Harada, M. Tanikawa, T. Iwabe, F. Taniguchi, and N. Terakawa
The potential role of stem cell factor and its receptor c-kit in the mouse blastocyst implantation
Mol. Hum. Reprod., September 1, 1999; 5(9): 874 - 879.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. Cohn, R. J. Homer, H. MacLeod, M. Mohrs, F. Brombacher, and K. Bottomly
Th2-Induced Airway Mucus Production Is Dependent on IL-4R{alpha}, But Not on Eosinophils
J. Immunol., May 15, 1999; 162(10): 6178 - 6183.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
D. Parichy, J. Rawls, S. Pratt, T. Whitfield, and S. Johnson
Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development
Development, January 8, 1999; 126(15): 3425 - 3436.
[Abstract] [PDF]


Home page
BloodHome page
M.-C. Labastie, F. Cortes, P.-H. Romeo, C. Dulac, and B. Peault
Molecular Identity of Hematopoietic Precursor Cells Emerging in the Human Embryo
Blood, November 15, 1998; 92(10): 3624 - 3635.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Z. Ratajczak, D. Perrotti, P. Melotti, M. Powzaniuk, B. Calabretta, K. Onodera, D. A. Kregenow, B. Machalinski, and A. M. Gewirtz
Myb and Ets Proteins Are Candidate Regulators of c-kit Expression in Human Hematopoietic Cells
Blood, March 15, 1998; 91(6): 1934 - 1946.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
V. C. Broudy
Stem Cell Factor and Hematopoiesis
Blood, August 15, 1997; 90(4): 1345 - 1364.
[Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. Sattler, R. Salgia, G. Shrikhande, S. Verma, E. Pisick, K. V.S. Prasad, and J. D. Griffin
Steel Factor Induces Tyrosine Phosphorylation of CRKL and Binding of CRKL to a Complex Containing c-Kit, Phosphatidylinositol 3-Kinase, and p120CBL
J. Biol. Chem., April 11, 1997; 272(15): 10248 - 10253.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. L. Miller, V. I. Rebel, C. D. Helgason, P. M. Lansdorp, and C. J. Eaves
Impaired Steel Factor Responsiveness Differentially Affects the Detection and Long-Term Maintenance of Fetal Liver Hematopoietic Stem Cells In Vivo
Blood, February 15, 1997; 89(4): 1214 - 1223.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
C. Nagamine and C Carlisle
The dominant white spotting oncogene allele Kit(W-42J) exacerbates XY(DOM) sex reversal
Development, January 11, 1996; 122(11): 3597 - 3605.
[Abstract] [PDF]


Home page
DevelopmentHome page
R Duttlinger, K Manova, T. Chu, C Gyssler, A. Zelenetz, R. Bachvarova, and P Besmer
W-sash affects positive and negative elements controlling c-kit expression: ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis
Development, January 7, 1993; 118(3): 705 - 717.
[Abstract] [PDF]


Home page
DevelopmentHome page
L Tessarollo, P Tsoulfas, D Martin-Zanca, D. Gilbert, N. Jenkins, N. Copeland, and L. Parada
trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues
Development, January 6, 1993; 118(2): 463 - 475.
[Abstract] [PDF]


Home page
Genes Dev.Home page
P Ray, K M Higgins, J C Tan, T Y Chu, N S Yee, H Nguyen, E Lacy, and P Besmer
Ectopic expression of a c-kitW42 minigene in transgenic mice: recapitulation of W phenotypes and evidence for c-kit function in melanoblast progenitors.
Genes & Dev., December 1, 1991; 5(12a): 2265 - 2273.
[Abstract] [PDF]


Home page
Genes Dev.Home page
A D Reith, R Rottapel, E Giddens, C Brady, L Forrester, and A Bernstein
W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor.
Genes & Dev., March 1, 1990; 4(3): 390 - 400.
[Abstract] [PDF]


Home page
ScienceHome page
J. Tan, K Nocka, P Ray, P Traktman, and P Besmer
The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase
Science, January 12, 1990; 247(4939): 209 - 212.
[Abstract] [PDF]


Home page
Genes Dev.Home page
K Nocka, S Majumder, B Chabot, P Ray, M Cervone, A Bernstein, and P Besmer
Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice.
Genes & Dev., June 1, 1989; 3(6): 816 - 826.
[Abstract] [PDF]