A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

Genome Biology

Steve DM Brown^1,12  Yann Herault¹  Martin Hrabě de Angelis^1,11  Ann-Marie Mallon^1,12  Karen P Steel⁶  Ramiro Ramirez-Solis⁶  Binnaz Yalcin¹  Min Zi⁸  Wolfgang Wurst⁷  Henrik Westerberg^1,12  Valerie E Vancollie⁶  Glauco P Tocchini-Valentini⁹  Anne Southwell^1,12  Carl Shannon⁶  Mohammed Selloum¹  Luis Santos^1,12  Mark Sanderson⁶  Jan Rozman^1,11  Laura-Anne Roberson⁶  Bastian Pasche⁵  George Nicholson^1,12  Frauke Neff^1,13  Werner Müller⁴  Hugh Morgan^1,12  Thomas M Keane⁶  Pierre Jurdic³  Tertius Hough^1,12  Sabine M Hölter^1,11  Wolfgang Hans^1,11  John M Hancock^1,12  Elisabetta Golini⁹  Anna-Karin Gerdin⁶  Hilary Gates^1,12  Armida di Fenza^1,12  Petr Danecek⁶  Roy Combe¹  Marie-France Champy¹  Heather Cater^1,12  Debra Brooker^1,12  Andrew Blake^1,12  Lore Becker^1,11  Abdel Ayadi¹  Sarah Atkins^1,12  David J Adams⁶  Michel Roux¹  Oliver Puk⁷  Frédéric Preitner²  Hamid Meziane¹  Jacqueline Marvel³  Silvia Mandillo⁹  Andreas Lengeling^1,14  Ian J Jackson^1,10  Neil J Ingham⁶  Jochen Graw⁷  Jeanne Estabel⁶  Sophia Djebali³  Romain Dacquin³  Elizabeth J Cartwright⁸  Elodie Bedu¹  Kim Wong⁶  Tania Sorg¹  Sara Wells^1,12  Valérie Gailus-Durner^1,11  Helmut Fuchs^1,11  Jacqueline K White⁶  Simon Greenaway^1,12  Michelle M Simon^1,12 

[1] Institut Clinique de la Souris, ICS/MCI, PHENOMIN, GIE CERBM, IGBMC, CNRS, INSERM, 1 Rue Laurent Fries, 67404 Illkirch-Graffenstaden Cedex, France;Department of Infection Genetics, Helmholtz Centre for Infection Research, Inhoffenstraße 7, Braunschweig, 38124, Germany;AniRA ImmOs phenotyping facility- SFR Biosciences Lyon Gerland- UMS3444/US8, 21 avenue Tony Garnier F-69007 Lyon, France;Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, MN13 9PT, UK;Mouse Metabolic Facility of the Cardiomet Center, University Hospital, and Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland;The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK;Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany;Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, MN13 9PT, UK;Consiglio Nazionale delle Ricerche- Cell Biology and Neurobiology Institute, Via E.Ramarini 32, 00015 Monterotondo Scala, Italy;Medical Research Council Human Genetics Unit, IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK;Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany;Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell Science Campus, OX11 0RD, UK;Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Pathology, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany;Infection and Immunity Division, Roslin Institute, University of Edinburgh, Easter Bush Veterinary Campus, Midlothian, EH25 9RG, UK

关键词: C57BL/6;    gene knockout;    mouse phenotyping;    sequence variation;    Mouse inbred lines;   

Others  :  864115
DOI  :  10.1186/gb-2013-14-7-r82

 received in 2013-03-18, accepted in 2013-07-31,  发布年份 2013

【 摘 要 】

Background

The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.

Results

We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.

Conclusions

Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

【 授权许可】

   
2013 Simon et al.; licensee BioMed Central Ltd.

【 图 表 】

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