Sex differences in genetic mechanisms for mammalian brain and behavior

Maxson, Stephen C.

doi:10.14748/bmr.v7.165

Cited by 11 publications

(4 citation statements)

References 53 publications

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“…Previous studies in mice have proved or suggested that the Y chromosome contains genes that influence various neural and behavioral traits, including aggressive behavior (Maxson et al, 1979;Maxson, 1992Maxson, , 1999Roubertoux et al, 1994;Guillot et al, 1995;Sluyter et al, 1996), the distribution of hippocampal mossy fibers (Hensbroek et al, 1995), dopamine systems , and brain serotonin (Tordjman et al, 1995). Moreover, Morris water maze learning performance has been reported to be more masculine in C57BL/6J XY POS female mice than in XX females (Stavnezer et al, 2000), although the fetal gonads of such females might contain some testicular tissue (Taketo et al, 1991), which could cause masculinization via a hormonal mechanism.…”

Section: Discussionmentioning

confidence: 99%

A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits

et al. 2002

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We tested the hypothesis that genes encoded on the sex chromosomes play a direct role in sexual differentiation of brain and behavior. We used mice in which the testis-determining gene (Sry) was moved from the Y chromosome to an autosome (by deletion of Sry from the Y and subsequent insertion of an Sry transgene onto an autosome), so that the determination of testis development occurred independently of the complement of X or Y chromosomes. We compared XX and XY mice with ovaries (females) and XX and XY mice with testes (males). These comparisons allowed us to assess the effect of sex chromosome complement (XX vs XY) independent of gonadal status (testes vs ovaries) on sexually dimorphic neural and behavioral phenotypes. The phenotypes included measures of male copulatory behavior, social exploration behavior, and sexually dimorphic neuroanatomical structures in the septum, hypothalamus, and lumbar spinal cord. Most of the sexually dimorphic phenotypes correlated with the presence of ovaries or testes and therefore reflect the hormonal output of the gonads. We found, however, that both male and female mice with XY sex chromosomes were more masculine than XX mice in the density of vasopressin-immunoreactive fibers in the lateral septum. Moreover, two male groups differing only in the form of their Sry gene showed differences in behavior. The results show that sex chromosome genes contribute directly to the development of a sex difference in the brain.

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Section: Discussionmentioning

confidence: 99%

A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits

et al. 2002

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“…Maxson compared aggressive behavior in congenic mouse strains that are genetically identical except for the alleles present on the Y chromosome 40. DBA/1 males are more aggressive than C57BL/10 males when they are tested in encounters with males of the same strain.…”

Section: Two Views Of Sexual Differentiationmentioning

confidence: 99%

Two Perspectives on the Origin of Sex Differences in the Brain

Arnold

Rissman

Vries

2003

Annals of the New York Academy of Sciences

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Most sex differences in brain function are attributed to sex differences in the effects of gonadal secretions. In addition, however, male and female cells differ because of differential effects of sex chromosome genes expressed within the cells themselves. The latter conclusion comes from numerous studies in which sexual phenotype appears to be insensitive to the effects of sex hormones during development or cases in which sex differences develop before the onset of sex-specific patterns of gonadal secretions. Recently, mouse models have become available in which the genetic sex of brain cells is independent of the gonadal type (testes vs. ovaries), which allows a test of the role of sex chromosome genes in brain development. This paper reviews the evidence that genetic sex of brain cells influences their sexual phenotype, and critically discusses the relative advantages of various experimental approaches to study this effect.

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“…In the early 1950s, the existence of a testis determining factor (TDF) on the Y chromosome, which initiates the masculinization of the genital ridge was predicted (see Jost et al 1973). Two candidate genes were SRY and ZFY, with the former being confirmed as TDF following mutation analysis in humans and due to its wide distribution across species (Maxson 1997, Marshall Graves 2000. SRY was first characterized and cloned by Sinclair et al (1990).…”

Section: Genetic Sexmentioning

confidence: 99%

“…This appears to be essential for normal functioning of the SRY gene, because sexual abnormalities are associated with HMG mutations (Fleming & Vilain 2004). Sex reversal can occur if the SRY gene is transposed onto the X chromosome or if it is absent from the Y chromosome; these abnormalities can occur naturally (Vilain & McCabe 1998) and more recently have been induced in mice experimentally, resulting in XY females and XX males (Maxson 1997, Arnold et al 2004. Although as yet unproven, it is thought that SRY together with SF1 as a synergistic factor, activates a cascade of other genes, which are required for development of the testis (Box 1).…”

Section: Genetic Sexmentioning

confidence: 99%

The control of sexual differentiation of the reproductive system and brain

Wilson¹,

Davies²

2007

Reproduction

160

116

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This review summarizes current knowledge of the genetic and hormonal control of sexual differentiation of the reproductive system, brain and brain function. While the chromosomal regulation of sexual differentiation has been understood for over 60 years, the genes involved and their actions on the reproductive system and brain are still under investigation. In 1990, the predicted testicular determining factor was shown to be the SRY gene. However, this discovery has not been followed up by elucidation of the actions of SRY, which may either stimulate a cascade of downstream genes, or inhibit a suppressor gene. The number of other genes known to be involved in sexual differentiation is increasing and the way in which they may interact is discussed. The hormonal control of sexual differentiation is well-established in rodents, in which prenatal androgens masculinize the reproductive tract and perinatal oestradiol (derived from testosterone) masculinizes the brain. In humans, genetic mutations have revealed that it is probably prenatal testosterone that masculinizes both the reproductive system and the brain. Sexual differentiation of brain structures and the way in which steroids induce this differentiation, is an active research area. The multiplicity of steroid actions, which may be specific to individual cell types, demonstrates how a single hormonal regulator, e.g. oestradiol, can exert different and even opposite actions at different sites. This complexity is enhanced by the involvement of neurotransmitters as mediators of steroid hormone actions. In view of current environmental concerns, a brief summary of the effects of endocrine disruptors on sexual differentiation is presented.

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Sex differences in genetic mechanisms for mammalian brain and behavior

Cited by 11 publications

References 53 publications

A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits

A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits

Two Perspectives on the Origin of Sex Differences in the Brain

The control of sexual differentiation of the reproductive system and brain

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