Radiosensitivity of Mice with Mutation at Loci W, Ph

SummaryA mutation to an apparently new allele at the W-locus of the mouse arose spontaneously in a cross between two inbred strains. Heterozygotes have a broad white sash, leading to the name and symbol sash, Wsh. Homozygotes are black-eyed whites which are viable, fertile and not anaemic, although the gene does cause mild haematopoietic defects. The original mutant animal also carried a spontaneous recessive lethal mutation on chromosome 5, mapping at 2 cM distal to the W-locus.

Section: Discussionmentioning

confidence: 82%

A new allele sash (W^sh) at theW-locus and a spontaneous recessive lethal in mice

Lyon¹,

Glenister²

1982

“…In W 19H + / + Rw there was a marginal reduction in RBC count (Loutit, in preparation). Despite the normal RBC count, radiosensitivity of W 1911 1 + is increased, the median lethal dose being 5-6 Gy, compared with a normal value of ~ 8 Gy (Loutit, Corp & Adams, 1982).…”

Section: Description Heterozygous W 19 "/ + Animals Typically Show MImentioning

confidence: 98%

A presumed deletion covering theWandPhloci of the mouse

Lyon¹,

Glenister²,

Loutit³

et al. 1984

A new allele at the >F-locus (W 19H ), found in a mutagenesis experiment in which females were irradiated, involves a presumed deletion. The deletion covers the Ph locus (which forms part of a gene complex with the W, Ph and Rw loci), and the locus of a recessive lethal 2 cM distal to W. It does not extend distally to the bl locus; nor does it involve the Rw locus, W 19H /Rw compounds being viable and fertile. Thus, the length of the deletion is 2-7 cM. The non-involvement of Rw shows that, in the gene triplet Rw, W, Ph, Rw must lie proximal to J^and Ph, whose relative position remains unknown. Heterozygotes for W 19 " are not anaemic, show only minimal white spotting and no pigment dilution; they thus resemble heterozygotes for the original W mutant allele and differ from W/Ph trans heterozygotes, which have extensive white spotting. In addition W 1911 heterozygotes may be small and runted, many are believed to die prenatally, and some in the nest. Their radiosensitivity is increased. Homozygotes die at the pre-implantation stage.

“…2) and microvascular incompetence with haemorrhage at doses of X-rays withstood by normal mice. The further exaggeration in double heterozygotes with Ph (Loutit et al 1982) is demonstrated again with the marked reduction (~ 2 Gy) of MLD when W ct + / + Ph is compared with W ct / + . Thus Ph must complement W* not only in erythropoiesis but in the various functions of the pluripotent stem cell.…”

Section: (Iii) X-irradiationmentioning

confidence: 85%

“…Dose-response to whole body X-irradiation. Normally + / + mice of the stock have a MLD of ~ 8 Gy (Loutit, Corp & Adams, 1982). Under similar conditions the responses of W ct /+ and W ct + / + Ph were as in Table 4.…”

Section: (Iii) X-irradiationmentioning

confidence: 98%

Haematopoietic role for Patch (Ph) revealed by newWmutant (W^ct) in mice

Loutit

Cattanach

1983

A new mutant (W ct ) has been identified at the W locus of the mouse. The homozygote is poorly viable. Whereas the heterozygote (W ct / +) is only mildly anaemic like W v / +, the double heterozygote W ct + / + Ph is considerably more anaemic than W v + / + Ph and it and W sh + / + Ph have significantly raised leucocyte counts. W ct + / + Ph is also unduly radiosensitive to whole body X-irradiation, 50% dying from haematopoietic failure at a dose of 4*59 + ()• 14 Gy,* whereas the median for W ct / + was 649 + 0-28 Gy. Serial blood counts of mice after low-or sub-lethal doses of X-rays revealed significantly more profound depression of counts of both red cells and leucocytes in W ct / + , and more notably in W ct +1 + Ph, than in + / + or W sh / 4-(haematologically normal) iso-dosed mice. We conclude that control of haematopoiesis by chromosome 5 is not confined to the W locus but is shared by the linked gene Ph (and perhaps Rw) and that expression of the change is not limited to the erythron but involves the pluripotent haematopoietic stem cell.