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

被引：381

作者：

Simon, Michelle M. ^{[1
,2
]}

Greenaway, Simon ^{[1
,2
]}

White, Jacqueline K. ^{[3
]}

Fuchs, Helmut ^{[4
,5
]}

Gailus-Durner, Valerie ^{[4
,5
]}

Wells, Sara ^{[1
,2
]}

Sorg, Tania ^{[8
]}

Wong, Kim ^{[3
]}

Bedu, Elodie ^{[8
]}

Cartwright, Elizabeth J. ^{[9
]}

Dacquin, Romain ^{[11
]}

Djebali, Sophia ^{[11
]}

Estabel, Jeanne ^{[3
]}

Graw, Jochen ^{[6
]}

Ingham, Neil J. ^{[3
]}

Jackson, Ian J. ^{[12
]}

Lengeling, Andreas ^{[13
]}

Mandillo, Silvia ^{[14
]}

Marvel, Jacqueline ^{[11
]}

Meziane, Hamid ^{[8
]}

Preitner, Frederic ^{[15
]}

Puk, Oliver ^{[6
]}

Roux, Michel ^{[8
]}

Adams, David J. ^{[3
]}

Atkins, Sarah ^{[1
,2
]}

Ayadi, Abdel ^{[8
]}

Becker, Lore ^{[4
,5
]}

Blake, Andrew ^{[1
,2
]}

Brooker, Debra ^{[1
,2
]}

Cater, Heather ^{[1
,2
]}

Champy, Marie-France ^{[8
]}

Combe, Roy ^{[8
]}

Danecek, Petr ^{[3
]}

di Fenza, Armida ^{[1
,2
]}

Gates, Hilary ^{[1
,2
]}

Gerdin, Anna-Karin ^{[3
]}

Golini, Elisabetta ^{[14
]}

Hancock, John M. ^{[1
,2
]}

Hans, Wolfgang ^{[4
,5
]}

Hoelter, Sabine M. ^{[4
,5
]}

Hough, Tertius ^{[1
,2
]}

Jurdic, Pierre ^{[11
]}

Keane, Thomas M. ^{[3
]}

Morgan, Hugh ^{[1
,2
]}

Mueller, Werner ^{[10
]}

Neff, Frauke ^{[7
]}

Nicholson, George ^{[1
,2
]}

Pasche, Bastian ^{[16
,17
]}

Roberson, Laura-Anne ^{[3
]}

Rozman, Jan ^{[4
,5
]}

机构：

[1] Med Res Council Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England

[2] Mary Lyon Ctr, Didcot OX11 0RD, Oxon, England

[3] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[4] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, D-85764 Neuherberg, Germany

[5] German Mouse Clin, D-85764 Neuherberg, Germany

[6] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany

[7] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Pathol, D-85764 Neuherberg, Germany

[8] INSERM, CNRS, IGBMC, Inst Clin Souris,ICS MCI,PHENOMIN,GIE CERBM, F-67404 Illkirch Graffenstaden, France

[9] Univ Manchester, Fac Med & Human Sci, Manchester MN13 9PT, Lancs, England

[10] Univ Manchester, Fac Life Sci, Oxford MN13 9PT, England

[11] AniRA ImmOs Phenotyping Facil, SFR Biosci Lyon Gerland, UMS3444 US8, F-69007 Lyon, France

[12] Univ Edinburgh, Western Gen Hosp, MRC, Human Genet Unit,IGMM, Edinburgh EH4 2XU, Midlothian, Scotland

[13] Univ Edinburgh, Roslin Inst, Infect & Immun Div, Roslin EH25 9RG, Midlothian, Scotland

[14] CNR, Cell Biol & Neurobiol Inst, Monterotondo Scala, I-00015 Monterotondo Scala, Italy

[15] Helmholtz Ctr Infect Res, Dept Infect Genet, D-38124 Braunschweig, Germany

[16] Univ Hosp Bern, Mouse Metab Facil, Cardiomet Ctr, CH-1015 Lausanne, Switzerland

[17] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland

[18] Tech Univ Munich, Chair Dev Genet, D-80333 Munich, Germany

[19] Max Planck Inst Psychiat, D-80804 Munich, Germany

[20] Deutsch Zentrum Neurodegenerat Erkrankungen, D-80336 Munich, Germany

来源：

GENOME BIOLOGY | 2013年 / 14卷 / 07期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

Mouse inbred lines; sequence variation; mouse phenotyping; gene knockout; C57BL/6; GENE; RESOURCE; EUROPHENOME; DATABASE; LINES; WIDE; CRB1;

D O I：

10.1186/gb-2013-14-7-r82

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

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.

引用

页数：22

共 36 条

[1] Cutting Edge: NLRP12 Controls Dendritic and Myeloid Cell Migration To Affect Contact Hypersensitivity [J].

Arthur, Janelle C. ;

Lich, John D. ;

Ye, Zhengmao ;

Allen, Irving C. ;

Gris, Denis ;

Wilson, Justin E. ;

Schneider, Monika ;

Roney, Kelly E. ;

O'Connor, Brian P. ;

Moore, Chris B. ;

Morrison, Amy ;

Sutterwala, Fayyaz S. ;

Bertin, John ;

Koller, Beverly H. ;

Liu, Zhi ;

Ting, Jenny P-Y. .

JOURNAL OF IMMUNOLOGY, 2010, 185 (08) :4515-4519

[2] Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium [J].

Brown, Steve D. M. ;

Moore, Mark W. .

DISEASE MODELS & MECHANISMS, 2012, 5 (03) :289-292

[3] Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes [J].

Carneiro, Ana M. D. ;

Airey, David C. ;

Thompson, Brent ;

Zhu, Chong-Bin ;

Lu, Lu ;

Chesler, Elissa J. ;

Erikson, Keith M. ;

Blakely, Randy D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (06) :2047-2052

[4] Predicting the Functional Effect of Amino Acid Substitutions and Indels [J].

Choi, Yongwook ;

Sims, Gregory E. ;

Murphy, Sean ;

Miller, Jason R. ;

Chan, Agnes P. .

PLOS ONE, 2012, 7 (10)

[5] Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse [J].

Church, Deanna M. ;

Goodstadt, Leo ;

Hillier, LaDeana W. ;

Zody, Michael C. ;

Goldstein, Steve ;

She, Xinwe ;

Bult, Carol J. ;

Agarwala, Richa ;

Cherry, Joshua L. ;

DiCuccio, Michael ;

Hlavina, Wratko ;

Kapustin, Yuri ;

Meric, Peter ;

Maglott, Donna ;

Birtle, Zoe ;

Marques, Ana C. ;

Graves, Tina ;

Zhou, Shiguo ;

Teague, Brian ;

Potamousis, Konstantinos ;

Churas, Christopher ;

Place, Michael ;

Herschleb, Jill ;

Runnheim, Ron ;

Forrest, Daniel ;

Amos-Landgraf, James ;

Schwartz, David C. ;

Cheng, Ze ;

Lindblad-Toh, Kerstin ;

Eichler, Evan E. ;

Ponting, Chris P. .

PLOS BIOLOGY, 2009, 7 (05)

[6] The Collaborative Cross, a community resource for the genetic analysis of complex traits [J].

Churchill, G ;

Airey, DC ;

Allayee, H ;

Angel, JM ;

Attie, AD ;

Beatty, J ;

Beavis, WD ;

Belknap, JK ;

Bennett, B ;

Berrettini, W ;

Bleich, A ;

Bogue, M ;

Broman, KW ;

Buck, KJ ;

Buckler, E ;

Burmeister, M ;

Chesler, EJ ;

Cheverud, JM ;

Clapcote, S ;

Cook, MN ;

Cox, RD ;

Crabbe, JC ;

Crusio, WE ;

Darvasi, A ;

Deschnepper, CF ;

Doerge, RW ;

Farber, CR ;

Forejt, J ;

Gaile, D ;

Garlow, SJ ;

Geiger, H ;

Gershenfeld, H ;

Gordon, T ;

Gu, J ;

Gu, WK ;

de Haan, G ;

Hayes, NL ;

Heller, C ;

Himmelbauer, H ;

Hitzemann, R ;

Hunter, K ;

Hsu, HC ;

Iraqi, FA ;

Ivandic, B ;

Jacob, HJ ;

Jansen, RC ;

Jjepsen, KJ ;

Johnson, DK ;

Johnson, TE ;

Kempermann, G .

NATURE GENETICS, 2004, 36 (11) :1133-1137

[7] A framework for variation discovery and genotyping using next-generation DNA sequencing data [J].

DePristo, Mark A. ;

Banks, Eric ;

Poplin, Ryan ;

Garimella, Kiran V. ;

Maguire, Jared R. ;

Hartl, Christopher ;

Philippakis, Anthony A. ;

del Angel, Guillermo ;

Rivas, Manuel A. ;

Hanna, Matt ;

McKenna, Aaron ;

Fennell, Tim J. ;

Kernytsky, Andrew M. ;

Sivachenko, Andrey Y. ;

Cibulskis, Kristian ;

Gabriel, Stacey B. ;

Altshuler, David ;

Daly, Mark J. .

NATURE GENETICS, 2011, 43 (05) :491-+

[8] 1977 RIETZ LECTURE - BOOTSTRAP METHODS - ANOTHER LOOK AT THE JACKKNIFE [J].

EFRON, B .

ANNALS OF STATISTICS, 1979, 7 (01) :1-26

[9] The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse [J].

Eppig, Janan T. ;

Blake, Judith A. ;

Bult, Carol J. ;

Kadin, James A. ;

Richardson, Joel E. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) :D881-D886

[10] RETRACTED: Nicotinamide nucleotide transhydrogenase: A key role in insulin secretion (Retracted article. See vol. 19, pg. 344, 2014) [J].

Freeman, H ;

Shimomura, K ;

Horner, E ;

Cox, RD ;

Ashcroft, FM .

CELL METABOLISM, 2006, 3 (01) :35-45

← 1 2 3 4 →