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E Simpson

Publications and source records attributed to E Simpson.

275 records · Page 16Linked to original sources
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Male sexual differentiation in mice lacking H-Y antigen.

The sexual phenotype of an adult mammal depends on whether the fetal gonad has differentiated as a testis or as an ovary. Because individuals of XY or XXY sex chromosome constitution develop as males, while XX and XO individuals develop as females, the presence of a Y chromosome seems normally to be required for testis differentiation and its absence to be necessary for differentiation of an ovary. The nature of the hypothetical Y-dependent substance responsible for masculinization of the indifferent gonad has been a matter for debate. A male-specific transplantation antigen, H-Y, has been known for many years and more recently a serologically detected antigen, also male-specific, has been reported. Those who believe that the two are antigenically distinct refer to the latter as SDM (serologically detected male) antigen, but many refer to both as H-Y antigen. The hypothesis that H-Y is itself the Y-dependent testis inducer, although supported by little or no direct evidence, is economical and hence attractive. H-Y antigen is frequently stated to be the substance responsible for primary sex determination (for example, see ref. 11). We report here that H-Y is absent from certain mice that develop testes and are of indisputably male phenotype, hence this transplantation antigen is unlikely to be responsible for testis determination.

Animals↗
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Separation of the genetic loci for the H-Y antigen and for testis determination on human Y chromosome.

The mammalian Y chromosome encodes a testis-determining factor (termed TDF in the human), a master regulator of sex differentiation. Embryos with a Y chromosome develop testes and become males whereas embryos lacking a Y chromosome develop ovaries and become females. Expression of H-Y, a minor histocompatibility antigen, may also be controlled by a gene on the Y chromosome, and it has been proposed that this antigen is the testis-determining factor. We have tested the postulated identity of H-Y and TDF in the human. H-Y typing with T cells was carried out on a series of sex-reversed humans (XX males and XY females), each shown by DNA hybridization to carry part but not all of the Y chromosome. This deletion analysis maps the gene for H-Y to the long arm or centromeric region of the human Y chromosome, far from the TDF locus, which maps to the distal short arm.

Chromosome Deletion↗
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H-Y responses of non-obese diabetic (NOD) mice.

Female non-obese diabetic (NOD) mice were tested for their ability to make responses to the male-specific (H-Y) transplantation antigen. In vivo assessment of this ability was made using skin graft rejection. A proportion (60%) spontaneously rejected NOD male tail skin by 80 days post-transplantation. The detection of the generation of H-Y-specific cytotoxic T cells, following in vivo priming and secondary in vitro restimulation, was carried out using a conventional 51Cr release assay. Female NOD mice primed either by skin grafting, intraperitoneal (i.p.) or footpad (f.p.) injection of male NOD spleen cells could be induced to make anti-H-Y cytotoxic responses, but not every immunized mouse responded. The nature of the H-Y-reactive T cells was investigated further by the in vitro isolation of T-cell clones of which some were H-Y specific.

Animals↗