Male, female and intersex development in mice of identical chromosome constitution

Cattanach, B.M.; Evans, E. P.; Burtenshaw, M. D.; Barlow, J.

doi:10.1038/300445a0

Cited by 71 publications

(22 citation statements)

References 16 publications

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“…These studies include: (1) the role of DNA methylation in X inactivation (Chapman et al, 1982;Kratzer et al, 1983); (2) the detection of genes escaping X inactivation (Agulnik et al, 1994;Wu et al, 1994) and those reactivated with aging (Wareham et al, 1987;Brown and Rastan, 1988); (3) an inquiry into the behavior of X-linked transgenes (Goldman et al, 1987;Wu et al, 1992;Tan et al, 1993); (4) analysis of X inactivation in germ cells (Johnston, 1981;Tam et al, 1994); and (5) neutralization of the sex-reversing potential of Sxr to produce fertile T16H/XSxr females (Cattanach et al, 1982;McLaren and Monk, 1982;McLaren, 1986). Taking advantage of the fact that the Xist gene is expressed exclusively from the inactivated X chromosome (Brockdorff et al, 1992;Brown et al, 1992), we decided to settle this problem because nonrandom inactivation, if verified, may throw new light on the regulatory mechanism of X inactivation.…”

Section: Introductionmentioning

confidence: 99%

Translocation breakpoint possibly predisposes to nonrandom X-chromosome inactivation in mouse embryos bearing Searle’s T(X;16)16H translocation

Ogura

Takada

Mise

et al. 1998

Cytogenet Genome Res

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To clarify the sequence of events that ultimately achieves the nonrandom inactivation of the paternally inherited X chromosome in postpartum female mice heterozygous for T(X;16)16H, we set out to examine the expression of Xist alleles and the X-linked HMG-lacZ transgene in embryos recovered at the egg cylinder stage. Lack of expression of the Xist^b allele on the 16^X translocation chromosome in the embryonic region of 7.5 d postcoitum (dpc) X¹⁶/XⁿXist^a;16^XXist^b/16 embryos strongly suggested the occurrence of nonrandom inactivation in favor of the normal X chromosome. The simplest explanation would be biased choice, followed by postinactivation selection against genetically unbalanced cells. However, the frequency and distribution of β-galactosidase-positive cells in X¹⁶/XⁿlacZ;16^X/16 embryos at 6.5 and 7.5 dpc, together with earlier cytogenetic data, raised an intriguing possibility that the majority of 16^X chromosomes were prevented from completing the inactivation process, when they had been chosen to be silenced. Phenotypes of female mice carrying a spontaneous recombination between Xⁿ and 16^X in the segment defined by the T16H breakpoint and the X-linked Ta locus suggested that the nonrandomness was brought about by disruption of an X-chromosomal sequence or structure at the translocation breakpoint.

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Section: Introductionmentioning

confidence: 99%

Translocation breakpoint possibly predisposes to nonrandom X-chromosome inactivation in mouse embryos bearing Searle’s T(X;16)16H translocation

Ogura

Takada

Mise

et al. 1998

Cytogenet Genome Res

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“…However, a nonrandom X-inactivation pattern can be brought about in X/XSxr animals using the T16H translocation [T(X;16)16H]. In some X(T16H)/XSxr individuals the Sxr region is inactivated with the result that female development occurs (7,8 …”

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confidence: 99%

Y chromosome short arm-Sxr recombination in XSxr/Y males causes deletion of Rbm and XY female sex reversal.

Laval

Glenister

Rasberry

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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We earlier described three lines of sexreversed XY female mice deleted for sequences believed close to the testes-determining gene (Sry) The mouse mutation sex reversed (Sxr) arose through a duplication of the Y chromosome short arm (Yp), including the sex-determining gene Sry and transposition to the pseudoautosomal region at the end of the Y long arm (1-3). In addition to Sry, Sxr contains all of the Y chromosome genes necessary for spermatogenesis up to the round spermatid stage (4) and all other known Yp genes including Zfyl, Zfy2, Ubelyl, and Smcy (5). Pseudoautosomal crossing-over in carrier (X/ YSxr) males transfers Sxr to the X chromosome, causing sex reversal of the X/XSxr progeny (6).Normally Sxr is transmitted only through X/YSxr males, as X/XSxr males are sterile. However, a nonrandom X-inactivation pattern can be brought about in X/XSxr animals using the T16H translocation [T(X;16)16H]. In some X(T16H)/XSxr individuals the Sxr region is inactivated with the result that female development occurs (7,8 10403The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…XX mice carrying the "sex-reversed" property (XSxr) develop as males (17). However, mice heterozygous for the XSxr chromosome and the Searle translocation (T16H/ XSxr) can be female (18,19) because the translocation is preferentially active and the Sxr-carrying X chromosome is inactive. This secondary sex reversal has been attributed to inactivation of the "male-determining Sxr sequences" (19) on the XSxr chromosome.…”

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Sex determination: a hypothesis based on noncoding DNA.

Chandra¹

1985

Proc. Natl. Acad. Sci. U.S.A.

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Certain recent models of sex determination in mammals, Drosophila melanogaster, Caenorhabditis ekgans, and snakes are examined in the light of the hypothesis that the relevant genetic regulatory mechanisms are similar and interrelated. The proposed key element in each of these instances is a noncoding DNA sequence, which serves as a high-affinity binding site for a repressor-like molecule regulating the activity of a major "sex-determining" gene. On this basis it is argued that, in several eukaryotes, (i) certain DNA sequences that are sex-determining are noncoding, in the sense that they are not the structural genes of a sex-determining protein; (it) in some species these noncoding sequences are present in one sex and absent in the other, while in others their copy number or accessibility to regulatory molecules is significantly unequal between the two sexes; and (fii) this inequality determines whether the embryo develops into a male or a female.Sex determination in Drosophila melanogaster (1-4) and Caenorhabditis elegans (5) appears to be based on interactions among a small number of genes, with the level of activity of one gene being of primary importance. Consequently, it becomes feasible to look upon the choice of sexual phenotype in development as being mediated through a kind of genetic switch that opens up one or the other of two alternative pathways. If so, one is then led to inquire about the nature of the regulatory elements that might constitute such a switch.If sex determination is based on a small number of critical genes and on an "either/or" mechanism, it is reasonable to expect both single-gene mutations and, occasionally, environmental perturbations to shift sexual development from one pathway to the other. Mutations that transform sex in this manner are known in D. melanogaster, in C. elegans, and in mammals. In some reptiles sex is determined by the temperature at which egg incubation occurs. The sharp temperature thresholds seen in these experiments (6, 7) and the absence of intersexes or significant egg mortality suggest that not only a small number of genes might be involved but also a high degree of cooperativity in the relevant regulatory processes.On the basis of a recent model for mammalian sex determination (8, 9) and related results (2), I wish to suggest that certain noncoding DNA sequences could be responsible for the choice of sexual phenotype during development. The term "noncoding" sequence is used in this paper to mean that the DNA sequence is not the structural gene for a sexdetermining protein. Rather, its role in sex determination is to bind a repressor-like molecule and, thereby, to regulate indirectly the activity of a "sex-determining" gene. "Repressor" denotes a regulatory molecule that has high affinity for the noncoding sequence(s) but whose primary role is in controlling the activity of a major sex-determining gene.THE MODELS Mammals. There are at least three observations that must be faced by any model of primary sex determination in mammals: (i) the failure...

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Male, female and intersex development in mice of identical chromosome constitution

Cited by 71 publications

References 16 publications

Translocation breakpoint possibly predisposes to nonrandom X-chromosome inactivation in mouse embryos bearing Searle’s T(X;16)16H translocation

Translocation breakpoint possibly predisposes to nonrandom X-chromosome inactivation in mouse embryos bearing Searle’s T(X;16)16H translocation

Y chromosome short arm-Sxr recombination in XSxr/Y males causes deletion of Rbm and XY female sex reversal.

Sex determination: a hypothesis based on noncoding DNA.

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