The International Journal of Developmental Biology

Int. J. Dev. Biol. 45: 513 - 518 (2001)

Vol 45, Issue 3

Special Issue: Mammalian Reproduction and Development

The case of the midwife scientist

Published: 1 May 2001

E Simpson

MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, England. elizabeth.simpson@csc.mrc.ac.uk

Abstract

Genes controlling both testis determining and expression of the male-specific transplantation antigen, HY, are located on the short arm of the mouse Y chromosome, and on the X and Y-linked translocation, Sxr(a). A mutation of Sxr(a) was discovered in a cross between an Sxr carrier male and a T16H/X female. This was designated Sxr(b) and found to affect both the expression of HY and spermatogenesis, but not testis differentiation, thereby disproving Ohno's hypothesis that HY controlled testis determination. Molecular genetic analysis showed the mutation to be caused by fusion of two duplicated genes, Zfy1 and Zfy2, deleting the intervening DNA. This deletion interval, deltaSxr(b), contained a number of genes, each a candidate HY gene. Expression cloning with HY-specific T cell clones identified Smcy, Uty and Dby as encoding peptide epitopes of this transplantation antigen. The human homologues SMCY and UTY likewise express HY antigens and these are targets of damaging graft-versus-host (GVH) responses and potentially therapeutic graft-versus-leukaemia (GVL) responses following bone marrow transplantation (BMT). Knowledge of the peptide identity of HY epitopes allows monitoring of immune responses following BMT, using fluorescent tetramers, and also offers the possibility of inducing immunological tolerance.

Full text in web format is not available for this article. Please download the PDF version.