Evidence map›Paper›PMID 41723549›Full record

ArticleBiology of sex differences2026

Sry-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more.

Arthur P Arnold, Xuqi Chen, Michael N Grzybowski, Janelle M Ryan, Dale R Sengelaub, Tara Mohanroy, V Andree Furlan, Helen R Schmidtke, Jeremy W Prokop, Monika Tutaj and 18 more

Abstract read
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In one paragraph

Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

  • Update of
    2025
5 · Who and what money

Authors and funding

28 authors.

Arthur P ArnoldDepartment of Integrative Biology & Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA. arnold@ucla.edu.
Xuqi ChenDepartment of Integrative Biology & Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Michael N GrzybowskiDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Janelle M RyanHudson Institute of Medical Research, Monash Medical Centre, Melbourne, Australia.
Dale R SengelaubDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Tara MohanroyDepartment of Integrative Biology & Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
V Andree FurlanDepartment of Integrative Biology & Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Helen R SchmidtkeDepartment of Integrative Biology & Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jeremy W ProkopOffice of Research, Corewell Health, Grand Rapids, MI, 49503, USA.
Monika TutajDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Julia L CiosekDepartment of Veterinary Science, Martin-Gatton College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY, 40546, USA.
Theodore S KalbfleischDepartment of Veterinary Science, Martin-Gatton College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY, 40546, USA.
Liza O'DonnellHudson Institute of Medical Research, Monash Medical Centre, Melbourne, Australia.
William GrishamDepartment of Psychology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Shanie LandenHudson Institute of Medical Research, Monash Medical Centre, Melbourne, Australia.
Lynn MalloyDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Akiko TakizawaDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Kai LiDepartment of Veterinary Science, Martin-Gatton College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY, 40546, USA.
Hayk BarseghyanCenter for Precision Medicine and Genomics Research, District of Columbia, Children's National Hospital, Washington, USA.
Carrie B WieseDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Laurent VergnesDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Karen ReueDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Jonathan WanagatDepartment of Medicine, Division of Geriatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Helen SkaletskyHoward Hughes Medical Institute, Whitehead Institute, Cambridge, MA, USA.
David C PageHoward Hughes Medical Institute, Whitehead Institute, Cambridge, MA, USA.
Vincent R HarleyHudson Institute of Medical Research, Monash Medical Centre, Melbourne, Australia.
Melinda R DwinellDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Aron M GeurtsDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.

Funding

Gene targeted rat resource for the study of complex diseaseR24HL114474 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI DWINELL, MELINDA R · 2013 to 2017
$8.7M
Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
The impact of estrogen receptor alpha on cardiomyocellular metabolism and healthU54HL170326 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Hooman Allayee · 2023 to 2026
$7.5M
Hybrid Rat Diversity Program - Import of HXB/BXH panelR24OD024617 · OD · MEDICAL COLLEGE OF WISCONSIN · PI DWINELL, MELINDA R · 2018 to 2025
$6.8M
Transformative rat models to study sex differences in diseaseR01OD030496 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, DWINELL, MELINDA R · 2021 to 2025
$3.1M
Sry transgenic rats for investigation of XX vs. XY differences in phenotypesR21OD026560 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, DWINELL, MELINDA R · 2018 to 2019
$440k
NHLBI NIH HHS R24 HL114474NHLBI NIH HHS U54 HL170326NIDDK NIH HHS U54 DK120342NIH HHS DK120342NIH HHS OD026560, OD030496NIH HHS OD026560, OD030496, HL114474, OD024617, HL064541NIH HHS OD030496NIH HHS R01 OD030496NIH HHS R21 OD026560NIH HHS R24 OD024617
6 · The paper itself

Abstract

backgroundPrevious research on Four Core Genotypes and XY* mice has been instrumental in establishing important effects of sex-chromosome complement that cause sex differences in physiology and disease. We have generated rat models using similar modifications of the testis-determining gene Sry, to produce XX and XY rats with the same type of gonad, as well as XO, XXY and XYY rats with varying gonads. The models permit discovery of novel sex-chromosome effects (XX vs. XY) that contribute to sex differences in any rat phenotype, and test for effects of different numbers of X or Y chromosomes.

methodsXY rats were created with an autosomal transgene of Sry, producing XX and XY progeny with testes. In other rats, CRISPR-Cas9 technology was used to remove Y chromosome factors that initiate testis differentiation, producing fertile XY gonadal females. Interbreeding of these lines produced rats with interesting combinations of sex chromosomes and gonads: XO, XX, XY, XXY rats with ovaries; and XO, XX, XY, XXY, and XYY rats with testes. These groups can be compared to detect sex differences caused by sex-chromosome complement (XX vs. XY) and/or by gonadal hormones (rats with testes vs. ovaries). Other comparisons detect the effects of X or Y chromosome number (in gonadal females: XO vs. XX, XX vs. XXY, XO vs. XY, XY vs. XXY; in gonadal males: XY vs. XXY, XY vs. XYY; XX vs. XXY, XO vs. XX, XO vs. XY).

resultsWe measured numerous phenotypes to characterize these models, including gonadal histology, breeding performance, anogenital distance, levels of reproductive hormones, body and organ weights, and central nervous system sexual dimorphisms. Serum testosterone levels were comparable in adult XX and XY gonadal males. Phenotypes previously known to be sexually differentiated by the action of gonadal hormones were found to be similar in XX and XY rats with the same type of gonad, suggesting that XX and XY rats with the same type of gonad have comparable levels of gonadal hormones at various stages of development.

conclusionThe results establish powerful new models to discriminate sex-chromosome and gonadal hormone effects that cause sex differences in rat physiology and disease.

Indexed as

Genes, srySex CharacteristicsSex-Determining Region Y ProteinAnimalsFemaleGenotypeMaleRatsRats, TransgenicTestisX ChromosomeY ChromosomeSex-Determining Region Y ProteinFour core genotypesGametogenesis.MeiosisSex-chromosome effectSex determinationSexual differentiationSryTestis determinationX chromosomeY chromosome

Identifiers

PMID41723549
PMCPMC13067745

What Socratic holds

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.