XY female mice resulting from a heritable mutation in the primary testis determining gene, Tdy
Abstract
Chimeric mice constructed with XY embryonic stem (ES) cells that had been multiply infected with a retroviral vector were used in a genetic screen to look for mutations affecting the sex determination pathway in mice. From a small number of chimeras screened one was identified that gave rise to a low proportion of XY females amongst his offspring. Analysis of the segregating patterns of retroviral insertions demonstrated that the mutation was found in a subset of the offspring derived from one originally infected ES cell. However, the mutation appeared to have occurred subsequent to the infection. Some of the XY females proved to be fertile, and the mutant phenotype was found to segregate exclusively with the Y chromosome. Analysis of the offspring also confirmed the absence of any retroviral insertion that could be correlated with the mutation. Further characterisation of the Y chromosome carrying the mutation by karyotypic analysis, and by Southern blotting with a range of Y-specific DNA probes suggested that there has been no gross deletion or rearrangement of the Y carrying the mutation. There also appeared to be no loss of Y-specific gene functions apart from that of testis determination. Moreover, the mutation is complemented by Sxr', the minimum portion of the mouse Y known to carry Tdy. From the phenotype and deduced location of the mutation, we conclude that it is within the Tdy locus. This is the first such mutation to be described in mice.
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The FCG mouse model allows for an independent assessment of gonadal hormones and sex chromosomal effects.
“we used the Four Core Genotypes (FCG) mouse model, which allows for an independent assessment of gonadal hormones and sex chromosomal effects [47–49].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [48]
In the FCG model, the Sry gene is excised from the Y chromosome and inserted into an autosome, creating four sex chromosome-gonad combinations: XX with ovaries (FCG XX), XY with ovaries (Tg XY−), XX with testes (Tg XXSry), or XY with testes (Tg XYSry).
“While the sex determining region Y (Sry) gene is required for male testes formation, in this mouse model, this gene is excised from the Y chromosome and inserted into an autosome, creating four sex chromosome-gonad combinations: XX with ovaries (FCG XX), XY with ovaries (Transgenic (Tg) XY−), XX with testes (Tg XXSry), or XY with testes (Tg XYSry) [48].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [48]
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- Authors
- Lovell-Badge, R., & Robertson, E.
- Affiliations
- National Institute for Medical Research (GB)
- Columbia University (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1990-07-01
- Volume
- 109
- Issue
- 3
- Pages
- 635-646
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2120585869
- Cited by
- 311
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 6 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 11 · 2014: 14 · 2013: 9 · 2012: 10
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- XY females, testis determination, sex determination, Y chromosome, chimeric mice, retroviral integration, embryonic stem cells, pregnane X receptor, inherited mutations, mouse genetics
- MeSH terms
- Animals, Chimera, DNA, Female, Genetic Vectors, Karyotyping, Mutation, Ovary, Retroviridae, Sex Chromosome Aberrations, Sex Determination Analysis, Y Chromosome, Blotting, Southern, Mice
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