Haematopoietic role for Patch (Ph) revealed by newWmutant (Wct) in mice

Loutit, J. F.; Cattanach, B.M.

doi:10.1017/s0016672300021467

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…In most instances, Ph complements alleles at the closely linked W locus and the associated rumpp-white (Rw) locus (7,23). Although Ph heterozygotes have no measurable effects on hematopoiesis, some Ph/W combinations show an enhancement of the hematological defects associated with W gene mutations (24). This interaction with W, which is specific to the patch-extended (Ph') allele, has also been shown to include the germ cells (25).…”

Section: Resultsmentioning

confidence: 99%

Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.

Stephenson

Mercola

Anderson

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

184

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Platelet-derived growth factor receptors are composed of two subunits (a and (3) that associate with one another to form three functionally active dimeric receptor species. The two subunits are encoded by separate loci in humans and other species. In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the a-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5. Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra. This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes. Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes). We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes. The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor a subunit during mammalian development.A series of semidominant mutations that cause white spotting in the mouse are closely linked to one another on chromosome 5. Included in this cluster are the loci for dominant spotting (W), patch (Ph), and rump-white (Rw)

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Section: Resultsmentioning

confidence: 99%

Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.

Stephenson

Mercola

Anderson

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

184

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“…Mutant alleles at the Ph locus also result in white spotting, and have effects on haematopoiesis and radio-sensitivity (Loutit & Cattanach, 1983); homozygotes for mutant alleles die in utero sometimes having a 'split-face' malformation. The W and Ph loci lie very close together with only a few rare crossovers ever having been reported (Griineberg & Truslove, 1960;Geissler et al 1981).…”

Section: Introductionmentioning

confidence: 99%

A presumed deletion covering theWandPhloci of the mouse

Lyon¹,

Glenister²,

Loutit³

et al. 1984

Genet. Res.

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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.

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“…the delay in recovery of RBC count normally seen with WV/ + (figure 2) and other typical W* heterozygotes (e.g. W'/ +, Loutit and Cattanach 1983) is not exaggerated but largely corrected by the presence of Spbl.…”

Section: 12mentioning

confidence: 74%

Radiation and Haematopoiesis in Harwell Steel Mice

Loutit

Peters

Searle

1986

International Journal of Radiation Biology and Related Studies

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Haematological information on steel (Sl) mice is limited largely to Sl/Sld mice of Bar Harbor stock (WC.B6 F1). Therefore, two Harwell alleles, SlgbH and Slcon, were investigated. In the steady state both heterozygotes were modestly anaemic, homozygous Slcon and compound Slcon/SlgbH more so. On perturbation by X-irradiation Slcon/SlgbH showed a decrease in median lethal dose (MLD)--6.5 Gy, Slcon/+ and Slcon/Slcon slightly less change (7.5 Gy) compared with +/+, 8 Gy. In recovery from sublethal doses single heterozygotes, double heterozygotes with Wv, and compounds showed no delay in restoration of the count of red blood corpuscles (RBC) such as that seen in typical W mice (e.g. Wv/+, W/Wv). Effects on Slcon/Slcon and Slcon/SlgbH differ from those reported for Sl/Sld in that they show normal growth of spleen colonies when used as lethally irradiated recipients of bone marrow, they support growth of implanted bone marrow to form radiation chimaeras. When Harwell steel mice are donors of bone marrow to lethally irradiated +/+ mice the chimaeras ultimately are not anaemic; when lethally irradiated Harwell steel mice are recipients of +/+ marrow they remain macrocytically anaemic. One deduces that, for normal development and production of normal RBC in the steady state, the erythron requires intrinsic factors determined by wild type alleles at the W locus and extrinsic factors determined by wild type alleles at the Sl locus. Mutant alleles at either locus may determine macrocytosis. Two mutant alleles at either locus are still more deleterious, often lethal. Whereas mutant W alleles may also influence the pluripotent haematopoietic stem cell (HSC) leading to reduced MLD on X-irradiation, a similarly reduced MLD for Sl mutants may represent an increased need for and consumption of products of the haematopoietic stem cells rather than truly increased radiosensitivity, since the Do for spleen colony-forming units is the same for Slcon/SlgbH as +/+ mice.

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

Cited by 5 publications

References 11 publications

Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.

Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.

A presumed deletion covering theWandPhloci of the mouse

Radiation and Haematopoiesis in Harwell Steel Mice

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