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.     

Spermatogenic failure in male mice lacking H-Y antigen

The mammalian Y chromosome carries a factor that initiates male sexual development by directing the fetal gonads to form testes. Wachtel and his colleagues proposed that this testis-determining function of the Y is mediated by the male-specific cell-surface antigen H-Y, originally defined by skin grafting. This attractive hypothesis, which has been widely accepted, was based on the assumption that serological tests using antisera raised against male cells were recognizing H-Y antigen. Although disputed this assumption is supported by some recent studies. However, mice have been described which develop testes but lack the cell-surface H-Y antigen as defined by T-cell-mediated transplantation tests. Thus, although it remains possible that a serologically detected male-specific antigen is responsible for testis determination, it seems that H-Y, as originally defined, is not. We show here that H-Y negative male mice, in losing the genetic information that encodes H-Y, have also lost genetic information required for spermatogenesis. This result identifies a gene on the mouse Y, distinct from the testis-determining gene, which is necessary for spermatogenesis, and raises the intriguing possibility that the product of this 'spermatogenesis gene' is H-Y antigen.     

Cytotoxic T-cell response to H-Y in 'non-responder' CBA mice

Murine cytotoxic T-cell (Tc cell) responses to various antigens are controlled by immune response genes (Ir) mapping in the major histocompatibility complex (H-2). Both helper T cells, controlled by I region-coded genes, and Tc cells, controlled by K/D antigens, are necessary for a positive response. An H-2-restricted Tc-cell response to the male specific minor transplantation antigen (H-Y) can be elicited in B10 (H-2b) female mice primed with syngeneic male spleen cells intraperitoneally (i.p.) or intravenously (i.v.), or by skin grafting followed by restimulation in vitro in mixed lymphocyte culture (MLR) with male cells. CBA (H-2k) mice do not respond by these routes of in vivo priming, and this was thought to be due to a lack of permissible Ir genes for helper function. However, we now report that subcutaneous hind-footpad (fp) immunisation of 'non-responder' CBA mice with syngeneic male cells changes them to responders, a result which argues against a generalised Ir gene-controlled helper defect.     

泥鳅和大鳞副泥鳅性腺细胞H－Y抗原的检测

以雄性小鼠脾细胞为抗原，免疫Ｂａｌｂ／ｃ小鼠，获得了高滴度的抗Ｈ－Ｙ抗原抗体．在此基础上，利用细胞毒性实验，对泥鳅和大鳞副泥鳅的性腺细胞进行了Ｈ－Ｙ抗原的检测．结果表明，泥鳅中雌雄性腺细胞均含有Ｈ－Ｙ抗原；大鳞副泥鳅中，Ｈ－Ｙ抗原仅存在于雌性性腺细胞中，提示其为ＺＺ／ＺＷ型性别决定．     

泥鳅和大鳞副泥鳅性腺细胞H－Y抗原的检测

以雄性小鼠脾细胞为抗原，免疫Ｂａｌｂ／ｃ小鼠，获得了高滴度的抗Ｈ－Ｙ抗原抗体．在此基础上，利用细胞毒性实验，对泥鳅和大鳞副泥鳅的性腺细胞进行了Ｈ－Ｙ抗原的检测．结果表明，泥鳅中雌雄性腺细胞均含有Ｈ－Ｙ抗原；大鳞副泥鳅中，Ｈ－Ｙ抗原仅存在于雌性性腺细胞中，提示其为ＺＺ／ＺＷ型性别决定．     

Sex ratio adjustment and kin discrimination in malaria parasites

Malaria parasites and related Apicomplexans are the causative agents of the some of the most serious infectious diseases of humans, companion animals, livestock and wildlife. These parasites must undergo sexual reproduction to transmit from vertebrate hosts to vectors, and their sex ratios are consistently female-biased. Sex allocation theory, a cornerstone of evolutionary biology, is remarkably successful at explaining female-biased sex ratios in multicellular taxa, but has proved controversial when applied to malaria parasites. Here we show that, as predicted by theory, sex ratio is an important fitness-determining trait and Plasmodium chabaudi parasites adjust their sex allocation in response to the presence of unrelated conspecifics. This suggests that P. chabaudi parasites use kin discrimination to evaluate the genetic diversity of their infections, and they adjust their behaviour in response to environmental cues. Malaria parasites provide a novel way to test evolutionary theory, and support the generality and power of a darwinian approach.     

Abnormal differentiation of thymocytes in mice treated with cyclosporin A

Cyclosporin A (CsA) acts as a powerful immunosuppressive agent, and also, when given in repeated doses, can cause T-cell-dependent graft-versus-host disease and organ-specific autoimmune disease in rodents. This suggests that CsA interferes with the processes governing self-tolerance, either by nullifying the activity of T suppressor cells or by preventing the deletion of autoreactive T cells during ontogeny in the thymus. We report here that irradiated mice given repeated injections of CsA show striking dysfunction of the thymus. There are two different effects, the first of which is that CsA seems to block the differentiation of immature CD4+CD8+ thymocytes into mature CD4+CD8- and CD4-CD8+ cells expressing a high density of T-cell receptors and CD3 molecules. Second, CsA-treated mice show incomplete deletion of T cells expressing T-cell receptor molecules reactive to self H-2 I-E molecules.