Sex reversal in the mouse (Mus musculus) is caused by a recurrent nonreciprocal crossover involving the X and an aberrant Y chromosome

The Y chromosome of Mus musculus poschiavinus interacts with the autosomal recessive gene tda-1b of the C57BL/6J laboratory strain of the house mouse to cause complete or partial sex reversal. Ovaries or ovotestes develop in a substantial proportion of the XY fetuses. Several different Y-specific DNA probes distinguish two major types of Y chromosome in the house mouse and they are represented by M. m. domesticus and M. m. musculus. The poschiavinus Y chromosome appears identical to the domesticus Y. The developmental distribution of the gonad types was examined in the first backcross or N2 generation of fetuses in C57BL/6J with six different domesticus-type Y chromosomes and, as controls, three different musculus-type Y chromosomes. Gonadal hermaphrodites were found with three of the six domesticus-type Y chromosomes. Both overall frequency and phenotypic distribution of types of gonadal hermaphrodites identify three classes of domesticus-type Y chromosome by their differential interaction with the C57BL/6J genetic background.Key words: mouse, Y chromosomes, gonadal hermaphrodites, primary sex determination.

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An Amino Acid Change in the DNA-Binding Region of Sry, found in Mus Musculus Domesticus and Other Species, does not Explain CS7BL/6J-yDOM Sex-Reversal

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(05)90001-6 ◽

1992 ◽

Vol 185 (1) ◽

pp. 310-316 ◽

Cited By ~ 7

Author(s):

Penelope E. Graves ◽

Robert P. Erickson

Keyword(s):

Amino Acid ◽

Dna Binding ◽

Mus Musculus ◽

Amino Acid Change ◽

Sex Reversal ◽

Mus Musculus Domesticus ◽

Binding Region

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Efficient TALEN-mediated gene knockin at the bovine Y chromosome and generation of a sex-reversal bovine

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03855-1 ◽

2021 ◽

Author(s):

Ming Wang ◽

ZhaoLin Sun ◽

Fangrong Ding ◽

Haiping Wang ◽

Ling Li ◽

...

Keyword(s):

Y Chromosome ◽

Nuclear Transfer ◽

Sex Reversal ◽

Practical Application ◽

Transcription Activator ◽

New Methods ◽

Fetal Fibroblasts ◽

Male Phenotype ◽

Solid Foundation ◽

First Time

AbstractFunctional elucidation of bovine Y-chromosome genes requires available genome editing technologies. Meanwhile, it has yet to be proven whether the bovine Sry gene is the main or single factor involved in the development of the male phenotype in bovine. Here, we efficiently knocked out four Y-linked genes (Sry, ZFY, DDX3Y, and EIF2S3Y) in bovine fetal fibroblasts (BFFs) with transcription activator-like effector nucleases (TALENs) individually. Furthermore, we used TALEN-mediated gene knockin at the Sry gene and generated a sex-reversal bovine by somatic cell nuclear transfer (SCNT). The resulting bovine had only one ovary and was sterile. We demonstrate, for the first time, that the Sry gene is an important sex-determining gene in bovine. Our method lays a solid foundation for detecting the biology of the bovine Y chromosome, as it may provide an alternative biological model system for the study of mammalian sex determination, and new methods for the practical application in agricultural, especially for sex predetermination.

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Defective Calmodulin-Mediated Nuclear Transport of the Sex-Determining Region of the Y Chromosome (SRY) in XY Sex Reversal

Molecular Endocrinology ◽

10.1210/me.2004-0334 ◽

2005 ◽

Vol 19 (7) ◽

pp. 1884-1892 ◽

Cited By ~ 39

Author(s):

Helena Sim ◽

Kieran Rimmer ◽

Sabine Kelly ◽

Louisa M. Ludbrook ◽

Andrew H. A. Clayton ◽

...

Keyword(s):

Y Chromosome ◽

Nuclear Import ◽

High Mobility ◽

Sex Reversal ◽

High Mobility Group ◽

Missense Mutations ◽

Nuclear Localization Signals ◽

Xy Sex Reversal

Abstract The sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, as mutations in SRY can cause XY sex reversal. Although some SRY missense mutations affect DNA binding and bending activities, it is unclear how others contribute to disease. The high mobility group domain of SRY has two nuclear localization signals (NLS). Sex-reversing mutations in the NLSs affect nuclear import in some patients, associated with defective importin-β binding to the C-terminal NLS (c-NLS), whereas in others, importin-β recognition is normal, suggesting the existence of an importin-β-independent nuclear import pathway. The SRY N-terminal NLS (n-NLS) binds calmodulin (CaM) in vitro, and here we show that this protein interaction is reduced in vivo by calmidazolium, a CaM antagonist. In calmidazolium-treated cells, the dramatic reduction in nuclear entry of SRY and an SRY-c-NLS mutant was not observed for two SRY-n-NLS mutants. Fluorescence spectroscopy studies reveal an unusual conformation of SRY.CaM complexes formed by the two n-NLS mutants. Thus, CaM may be involved directly in SRY nuclear import during gonadal development, and disruption of SRY.CaM recognition could underlie XY sex reversal. Given that the CaM-binding region of SRY is well-conserved among high mobility group box proteins, CaM-dependent nuclear import may underlie additional disease states.

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Roles of Anti-Müllerian hormone (Amh) and its duplicates in sex determination and germ cell proliferation of Nile tilapia

Genetics ◽

10.1093/genetics/iyab237 ◽

2021 ◽

Author(s):

Xingyong Liu ◽

Shengfei Dai ◽

Jiahong Wu ◽

Xueyan Wei ◽

Xin Zhou ◽

...

Keyword(s):

Cell Proliferation ◽

Sex Determination ◽

Germ Cell ◽

Y Chromosome ◽

X Chromosome ◽

Nile Tilapia ◽

Critical Period ◽

Sex Reversal ◽

Homozygous Mutation ◽

Germ Cell Proliferation

Abstract Duplicates of amh are crucial for fish sex determination and differentiation. In Nile tilapia, unlike in other teleosts, amh is located on X chromosome. The Y chromosome amh (amh△-y) is mutated with 5 bp insertion and 233 bp deletion in the coding sequence, and tandem duplicate of amh on Y chromosome (amhy) has been identified as the sex determiner. However, the expression of amh, amh△-y and amhy, their roles in germ cell proliferation and the molecular mechanism of how amhy determines sex is still unclear. In this study, expression and functions of each duplicate were analyzed. Sex reversal occurred only when amhy was mutated as revealed by single, double and triple mutation of the three duplicates in XY fish. Homozygous mutation of amhy in YY fish also resulted in sex reversal. Earlier and higher expression of amhy/Amhy was observed in XY gonads compared with amh/Amh during sex determination. Amhy could inhibit the transcription of cyp19a1a through Amhr2/Smads signaling. Loss of cyp19a1a rescued the sex reversal phenotype in XY fish with amhy mutation. Interestingly, mutation of both amh and amhy in XY fish or homozygous mutation of amhy in YY fish resulted in infertile females with significantly increased germ cell proliferation. Taken together, these results indicated that up-regulation of amhy during the critical period of sex determination makes it the sex-determining gene, and it functions through repressing cyp19a1a expression via Amhr2/Smads signaling pathway. Amh retained its function in controlling germ cell proliferation as reported in other teleosts, while amh△-y was nonfunctionalized.

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Fertile females of the mole Talpa occidentalis are phenotypic intersexes with ovotestes

Development ◽

10.1242/dev.118.4.1303 ◽

1993 ◽

Vol 118 (4) ◽

pp. 1303-1311 ◽

Cited By ~ 1

Author(s):

R. Jimenez ◽

M. Burgos ◽

A. Sanchez ◽

A.H. Sinclair ◽

F.J. Alarcon ◽

...

Keyword(s):

Y Chromosome ◽

Sex Reversal ◽

Chromosome Gene ◽

Different Populations ◽

Testis Determining Gene

We investigated the origin of XX sex reversal in the insectivorous mole Talpa occidentalis. Cytogenetic, histological and hormonal studies indicate that all XX individuals analyzed from two different populations are true hermaphrodites, with ovotestes. This suggests that XX sex reversal may be the norm in this species. The intersexes are functional fertile females and the trait is transmitted and maintained in the population. Intersexes lack the Y chromosome gene SRY (sex determining region Y gene), shown to be the testis determining gene. These results suggest that XX intersex moles may have arisen from a mutation of a gene located downstream from SRY/TDY in the testis determining pathway.

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Role of mammalian Y chromosome in sex determination

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1988.0114 ◽

1988 ◽

Vol 322 (1208) ◽

pp. 63-72 ◽

Cited By ~ 34

Keyword(s):

Cell Differentiation ◽

Sex Determination ◽

Y Chromosome ◽

Sertoli Cell ◽

Sertoli Cells ◽

Sex Reversal ◽

Testicular Development ◽

Chimeric Mouse ◽

Embryonic Gonad

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.

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Two types of mouse (Mus musculus domesticus) Y chromosomes in Quebec

Genome ◽

10.1139/g92-078 ◽

1992 ◽

Vol 35 (3) ◽

pp. 534-537

Author(s):

Yutaka Nishioka

Keyword(s):

Y Chromosome ◽

House Mouse ◽

Mus Musculus ◽

Repetitive Sequence ◽

The Other ◽

Chromosome Polymorphism ◽

Mus Musculus Domesticus ◽

Y Chromosomes

A Y chromosomal repetitive sequence identified two types of Y chromosomes in mice (Mus musculus domesticus) caught near Ste. Anne de Bellevue, Quebec. One type is apparently identical to the Y chromosome found in Maryland, Delaware, and California, whereas the other type is similar, but not identical, to the Y chromosome present in M.m. poschiavinus, an Alpine race of M.m. domesticus. These findings suggest that the domesticus Y chromosome is highly polymorphic and thus useful for elucidating the relationships among American and European house mouse populations.Key words: mouse Y chromosome, polymorphism, Mus musculus domesticus, repetitive sequence, Quebec.

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Mapping the human Y chromosome

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1988.0120 ◽

1988 ◽

Vol 322 (1208) ◽

pp. 125-131 ◽

Cited By ~ 4

Keyword(s):

Y Chromosome ◽

Dna Sequences ◽

Physical Map ◽

Sex Reversal ◽

Chromosomal Anomalies ◽

Deletion Mapping ◽

Molecular Analyses ◽

Large Size ◽

Definition Of ◽

Human Y Chromosome

This paper reviews past and present trends in mapping the human Y chromosome. So far, mapping has essentially used a combination of cytogenetic and molecular analyses of Y-chromosomal anomalies and sex reversal syndromes. This deletion mapping culminated recently in the isolation of the putative sex-determining locus TDF . With the availability of new separation and cloning techniques suited for large size fragments (over 100 kilobases), the next step will consist rather in the establishment of a physical map of fragments of known physical sizes. This may allow the definition of several variants of the human Y chromosome differing by the order or location of DNA sequences along the molecule.

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