Prevalence of sexual dimorphism in mammalian phenotypic traits.

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Abstract

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.

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Sex bias in neuroscience and biomedical research.

Annaliese Beery, Irving H. Zucker (2011)

Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex. Copyright © 2010 Elsevier Ltd. All rights reserved.

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Genetics of mouse behavior: interactions with laboratory environment.

J Crabbe, D Wahlsten, B C Dudek (1999)

Strains of mice that show characteristic patterns of behavior are critical for research in neurobehavioral genetics. Possible confounding influences of the laboratory environment were studied in several inbred strains and one null mutant by simultaneous testing in three laboratories on a battery of six behaviors. Apparatus, test protocols, and many environmental variables were rigorously equated. Strains differed markedly in all behaviors, and despite standardization, there were systematic differences in behavior across labs. For some tests, the magnitude of genetic differences depended upon the specific testing lab. Thus, experiments characterizing mutants may yield results that are idiosyncratic to a particular laboratory.

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A conditional knockout resource for the genome-wide study of mouse gene function.

William C. Skarnes, Barry Rosen, Anthony P. West … (2011)

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.

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Author and article information

Journal

Journal ID (iso-abbrev): Nat Commun

Title: Nature communications

Publisher: Springer Science and Business Media LLC

ISSN (Electronic): 2041-1723

ISSN (Print): 2041-1723

Publication date (Electronic): June 26 2017

Volume: 8

Affiliations

[1 ] Mouse Informatics Group, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

[2 ] Quantitative Biology, AstraZeneca, Unit 310, Cambridge Science Park, Cambridge CB4 0WG, UK.

[3 ] European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

[4 ] Human and Molecular Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA.

[5 ] Department of Statistics and O.R. School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

[6 ] Mouse Biology Program, University of California, 2795 Second Street, Suite 400, Davis, California 95618, USA.

[7 ] The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.

[8 ] MRC Harwell Institute, Harwell Campus, Harwell OX11 0RD, UK.

[9 ] Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA.

[10 ] The Centre for Phenogenomics, 25 Orde Street, Toronto, Ontario, Canada M5T 3H7.

[11 ] German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.

[12 ] School of Life Science Weihenstephan, Technische Universität München, Alte Akademie 8, Freising 85354, Germany.

[13 ] German Center for Diabetes Research (DZD), Ingostädter Landstr. 1, Neuherberg 85764, Germany.

[14 ] Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou, Nanjing, Jiangsu 210061, China.

[15 ] CELPHEDIA, PHENOMIN, Institut Clinique de la Souris, 1 Rue Laurent Fries, Illkirch 67404, France.

[16 ] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, Illkirch 67404, France.

[17 ] Centre National de la Recherche Scientifique, UMR7104, 1 rue Laurent Fries, Illkirch 67404, France.

[18 ] Institut National de la Santé et de la Recherche Médicale, U964, 1 rue Laurent Fries, Illkirch 67404, France.

[19 ] Université de Strasbourg, 1 rue Laurent Fries, Illkirch 67404, France.

[20 ] The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.

[21 ] Mouse Genetics Project, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

[22 ] Department of Genetics, Evolution &Environment, University College London, Gower Street, London WC1E 6BT, UK.

[23 ] BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.

[24 ] The Hospital for Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.

[25 ] Genetics Institute, University College London, Gower Street, London WC1E 6BT, UK.

[26 ] Clinical Pharmacology, Queen Mary University of London, Gower Street, London WC1E 6BT, UK.

[27 ] Wolfson Centre for Age-Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guys Campus, London SE1 1UL, UK.

[28 ] Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, California 94609, USA.

Article

Publisher Item ID: ncomms15475

DOI: 10.1038/ncomms15475

PMC ID: 5490203

PubMed ID: 28650954

SO-VID: 3003dd28-3952-4387-9ba4-06140838b54b

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Prevalence of sexual dimorphism in mammalian phenotypic traits.

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Most cited references 35

Sex bias in neuroscience and biomedical research.

Genetics of mouse behavior: interactions with laboratory environment.

A conditional knockout resource for the genome-wide study of mouse gene function.

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Cited by 107

Most referenced authors 787