Author
John Gubbay
Other affiliations: Rockefeller University
Bio: John Gubbay is an academic researcher from National Institute for Medical Research. The author has contributed to research in topics: Y chromosome & Mutant. The author has an hindex of 6, co-authored 8 publications receiving 3967 citations. Previous affiliations of John Gubbay include Rockefeller University.
Papers
More filters
••
TL;DR: It is shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
Abstract: The initiation of male development in mammals requires one or more genes on the Y chromosome. A recently isolated gene, termed SRY in humans and Sry in mouse, has many of the genetic and biological properties expected of a Y-located testis-determining gene. It is now shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
2,070 citations
••
TL;DR: A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination.
Abstract: A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.
1,604 citations
••
TL;DR: Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat.
Abstract: The testis-determining gene Sry is located on the short arm of the mouse Y chromosome in a region known to have undergone duplications and rearrangements in comparison with the equivalent portion of the human Y chromosome. Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat. This repeat, which is found in both Mus musculus musculus and Mus musculus domesticus Y chromosomes, is not present at the human SRY locus. Recombination involving the repeat region may have led to an 11-kilobase deletion, precisely excising Sry in a line of XY female mice.
197 citations
••
TL;DR: It is reported here that ZFY-1 but not Zfy-2 is expressed in differentiating embryonic mouse testes, and these observations exclude bothZfy-1 and Zfy -2 as candidates for the mouse testis-determining gene.
Abstract: The Y chromosome determines maleness in mammals. A Y chromosome-linked gene diverts the indifferent embryonic gonad from the default ovarian pathway in favour of testis differentiation, initiating male development. Study of this basic developmental switch requires the isolation of the testis-determining gene, termed TDF in humans and Tdy in mice. ZFY, a candidate gene for TDF, potentially encodes a zinc-finger protein, and has two Y-linked homologues, Zfy-1 and Zfy-2, in mice. Although ZFY, Zfy-1 and Zfy-2 seem to map to the sex-determining regions of the human and mouse Y chromosomes, there is no direct evidence that these genes are involved in testis determination. We report here that Zfy-1 but not Zfy-2 is expressed in differentiating embryonic mouse testes. Neither gene, however, is expressed in We/We mutant embryonic testes which lack germ cells. These observations exclude both Zfy-1 and Zfy-2 as candidates for the mouse testis-determining gene.
179 citations
••
TL;DR: Southern blot analysis is used to show that the Zfy genes have not undergone any major structural alterations, and it is demonstrated that both genes are transcribed normally from the mutant Y chromosome (Y) in both adult XYY testis and XY female embryonic gonads.
Abstract: Zfy-1 and Zfy-2 are candidate genes for Tdy, the testis-determining gene in mice. We have analysed these genes in a line of XY female mice that have been shown to be mutated in Tdy. We have used Southern blot analysis to show that the Zfy genes have not undergone any major structural alterations, and have also demonstrated that both genes are transcribed normally from the mutant Y chromosome (Y) in both adult XYY testis and XY female embryonic gonads. The fact that these genes show a normal structure and expression pattern in mice with a Y chromosome known to carry a mutation in Tdy and that mutant embryos develop into females despite Zfy-1 expression, strongly supports other recent evidence that Zfy genes are not directly involved in primary testis determination.
56 citations
Cited by
More filters
••
TL;DR: A search of a 35-kilobase region of the human Y chromosome necessary for male sex determination has resulted in the identification of a new gene, termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-d determining gene, TDF.
Abstract: A search of a 35-kilobase region of the human Y chromosome necessary for male sex determination has resulted in the identification of a new gene. This gene is conserved and Y-specific among a wide range of mammals, and encodes a testis-specific transcript. It shares homology with the mating-type protein, Mc, from the fission yeast Schizosaccharomyces pombe and a conserved DNA-binding motif present in the nuclear high-mobility-group proteins HMG1 and HMG2. This gene has been termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-determining gene, TDF.
3,019 citations
••
TL;DR: The lability of sex-determination systems in fish makes some species sensitive to environmental pollutants capable of mimicking or disrupting sex hormone actions, and such observations provide important insight into potential impacts from endocrine disruptors, and can provide useful monitoring tools for impacts on aquatic environments.
2,283 citations
••
TL;DR: It is shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
Abstract: The initiation of male development in mammals requires one or more genes on the Y chromosome. A recently isolated gene, termed SRY in humans and Sry in mouse, has many of the genetic and biological properties expected of a Y-located testis-determining gene. It is now shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
2,070 citations
••
TL;DR: Using TRPA1-deficient mice, it is shown that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain.
1,748 citations
••
TL;DR: A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination.
Abstract: A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.
1,604 citations