The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation

Abstract The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome...

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Main Authors: Carrie B. Wiese, Barbara Soliman, Karen Reue
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Biology of Sex Differences
Subjects:
Online Access:https://doi.org/10.1186/s13293-024-00665-5
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author Carrie B. Wiese
Barbara Soliman
Karen Reue
author_facet Carrie B. Wiese
Barbara Soliman
Karen Reue
author_sort Carrie B. Wiese
collection DOAJ
description Abstract The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimer’s and other diseases. A recent study determined that the Y Sry− chromosome used in a specific line of C57BL/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the Y Sry− translocation, and (4) delineate expression levels of the nine translocated genes across tissue/cell types as a filter for evaluating their potential involvement in specific phenotypes.
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spelling doaj-art-289e77a2d02b46d69650216b61ce2d812025-08-20T02:18:24ZengBMCBiology of Sex Differences2042-64102024-10-011511910.1186/s13293-024-00665-5The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocationCarrie B. Wiese0Barbara Soliman1Karen Reue2Department of Human Genetics, David Geffen School of Medicine, University of CaliforniaDepartment of Human Genetics, David Geffen School of Medicine, University of CaliforniaDepartment of Human Genetics, David Geffen School of Medicine, University of CaliforniaAbstract The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimer’s and other diseases. A recent study determined that the Y Sry− chromosome used in a specific line of C57BL/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the Y Sry− translocation, and (4) delineate expression levels of the nine translocated genes across tissue/cell types as a filter for evaluating their potential involvement in specific phenotypes.https://doi.org/10.1186/s13293-024-00665-5Sex differencesX chromosomeY chromosomeXY* mouse modelGene expression
spellingShingle Carrie B. Wiese
Barbara Soliman
Karen Reue
The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
Biology of Sex Differences
Sex differences
X chromosome
Y chromosome
XY* mouse model
Gene expression
title The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
title_full The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
title_fullStr The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
title_full_unstemmed The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
title_short The Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation
title_sort four core genotypes mouse model evaluating the impact of a recently discovered translocation
topic Sex differences
X chromosome
Y chromosome
XY* mouse model
Gene expression
url https://doi.org/10.1186/s13293-024-00665-5
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