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A chromosomal inversion predicts the expression of sex steroid-related genes in a species with alternative behavioral phenotypes.

ABSTRACT: In white-throated sparrows, a chromosomal rearrangement has led to alternative phenotypes that differ in sex steroid-dependent behaviors. The rearrangement has captured the genes estrogen receptor alpha and 5-alpha reductase, making these genes strong candidates for mediating the behavioral phenotypes. We report here that of the two genes, expression of estrogen receptor alpha mRNA differs between the morphs and predicts behavior to a much greater extent than does expression of 5-alpha reductase mRNA. Differentiation of estrogen receptor alpha, therefore, is likely more important for the behavioral phenotypes. We also found that in some brain regions, the degree to which testosterone treatment affects the expression of steroid-related genes depends strongly on morph. A large morph difference in estrogen receptor alpha mRNA expression in the amygdala appears to be independent of plasma testosterone; this difference persists during the non-breeding season and is detectable in nestlings at post-hatch day seven. The latter result suggests a substrate for organizational effects of hormones during development.

SUBMITTER: Grogan KE

PROVIDER: S-EPMC6749608 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A chromosomal inversion predicts the expression of sex steroid-related genes in a species with alternative behavioral phenotypes.

Grogan Kathleen E KE Horton Brent M BM Hu Yuchen Y Maney Donna L DL

Molecular and cellular endocrinology 20190723

In white-throated sparrows, a chromosomal rearrangement has led to alternative phenotypes that differ in sex steroid-dependent behaviors. The rearrangement has captured the genes estrogen receptor alpha and 5-alpha reductase, making these genes strong candidates for mediating the behavioral phenotypes. We report here that of the two genes, expression of estrogen receptor alpha mRNA differs between the morphs and predicts behavior to a much greater extent than does expression of 5-alpha reductase ...[more]

PMID: 31348983

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Project description:Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relevant to human disease is unclear. Here we show that in AD mouse models that overexpress amyloid precursor protein (APP) under control of the prion protein promoter (PrP), female transgenic mice have higher APP expression than males, complicating interpretations of the role of sex-related factors in such models. By contrast, in a tTa:APPsi model, in which APP expression is driven by the tetracycline transactivator (tTa) from the CaMKIIα promoter, there are no sex-related differences in expression or processing of APP. In addition, the levels of Aβ dimers and tetramers, as well as Aβ peptide accumulation, are similar between sexes. Behavioral testing demonstrated that both male and female tTa:APPsi mice develop age-dependent deficits in spatial recognition memory and conditional freezing to context. These cognitive deficits were accompanied by habituation-associated hyperlocomotion and startle hyper-reactivity. Significant sex-related dimorphisms were observed, due to females showing earlier onsets of the deficits in conditioned freezing and hyperlocomotion. In addition, tTa:APPsi males but not females demonstrated a lack of novelty-induced activation. Both males and females showed atrophy of the dentate gyrus (DG) of the dorsal hippocampus, associated with widening of the pyramidal layer of the CA1 area in both sexes. Ventral DG was preserved. Sex-related differences were limited to the DG, with females showing more advanced degeneration than males. Collectively, our data show that the tTa:APPsi model is characterized by a lack of sex-related differences in APP expression, making this model useful in deciphering the mechanisms of sex differences in AD pathogenesis. Sex-related dimorphisms observed in this model under conditions of equal APP expression between sexes suggest a higher sensitivity of females to the effects of APP and/or Aβ production.

Dataset Information

A chromosomal inversion predicts the expression of sex steroid-related genes in a species with alternative behavioral phenotypes.

Publications

A chromosomal inversion predicts the expression of sex steroid-related genes in a species with alternative behavioral phenotypes.

Similar Datasets

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