title: A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.
abstract: 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.
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authors.forename: Simon
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authors.lastname: Greenaway
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.forename: Helmut
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authors.lastname: Fuchs
authors.forename: Valérie
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authors.lastname: Gailus-Durner
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authors.lastname: Wells
authors.forename: Tania
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authors.forename: Elodie
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authors.forename: Jochen
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authors.lastname: Atkins
authors.forename: Abdel
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authors.lastname: Ayadi
authors.forename: Lore
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authors.lastname: Becker
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authors.lastname: Blake
authors.forename: Debra
authors.initials: D
authors.lastname: Brooker
authors.forename: Heather
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authors.lastname: Cater
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Champy
authors.forename: Roy
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authors.lastname: Combe
authors.forename: Petr
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authors.lastname: Danecek
authors.forename: Armida
authors.initials: A
authors.lastname: di Fenza
authors.forename: Hilary
authors.initials: H
authors.lastname: Gates
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Gerdin
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Golini
authors.forename: John M
authors.initials: JM
authors.lastname: Hancock
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.forename: Tertius
authors.initials: T
authors.lastname: Hough
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Keane
authors.forename: Hugh
authors.initials: H
authors.lastname: Morgan
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.forename: George
authors.initials: G
authors.lastname: Nicholson
authors.forename: Bastian
authors.initials: B
authors.lastname: Pasche
authors.forename: Laura-Anne
authors.initials: LA
authors.lastname: Roberson
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Mark
authors.initials: M
authors.lastname: Sanderson
authors.forename: Luis
authors.initials: L
authors.lastname: Santos
authors.forename: Mohammed
authors.initials: M
authors.lastname: Selloum
authors.forename: Carl
authors.initials: C
authors.lastname: Shannon
authors.forename: Anne
authors.initials: A
authors.lastname: Southwell
authors.forename: Glauco P
authors.initials: GP
authors.lastname: Tocchini-Valentini
authors.forename: Valerie E
authors.initials: VE
authors.lastname: Vancollie
authors.forename: Henrik
authors.initials: H
authors.lastname: Westerberg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Min
authors.initials: M
authors.lastname: Zi
authors.forename: Binnaz
authors.initials: B
authors.lastname: Yalcin
authors.forename: Ramiro
authors.initials: R
authors.lastname: Ramirez-Solis
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Mallon
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Yann
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authors.lastname: Herault
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authors.lastname: Brown
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D060467:Disease Resistance / Q000276:immunology; D005123:Eye / Q000473:pathology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D016678:Genome / Q000235:genetics*; D006967:Hypersensitivity / Q000276:immunology; D054643:INDEL Mutation / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008297:Male; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013154:Spleen / Q000276:immunology; D055114:X-Ray Microtomography
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