title: Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice.
abstract: BACKGROUND
  Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder and major depression. Several previous studies reported that mice with N-ethyl-N-nitrosourea (ENU)-induced L100P mutation in Disc1 showed some schizophrenia-related behavioral phenotypes. This line originally carried several thousands of ENU-induced point mutations in the C57BL/6 J strain and single nucleotide polymorphisms (SNPs) from the DBA/2 J inbred strain.
  
  
  METHODS
  To investigate the effect of Disc1 L100P, background mutations and SNPs on phenotypic characterization, we performed behavioral analyses to better understand phenotypes of Disc1 L100P mice and comprehensive genetic analyses using whole-exome resequencing and SNP panels to map ENU-induced mutations and strain-specific SNPs, respectively.
  
  
  RESULTS
  We found no differences in spontaneous or methamphetamine-induced locomotor activity, sociability or social novelty preference among Disc1 L100P/L100P, L100P/+ mutants and wild-type littermates. Whole-exome resequencing of the original G1 mouse identified 117 ENU-induced variants, including Disc1 L100P per se. Two females and three males from the congenic L100P strain after backcrossing to C57BL/6 J were deposited to RIKEN BioResource Center in 2008. We genotyped them with DBA/2 J × C57BL/6 J SNPs and found a number of the checked SNPs still remained.
  
  
  CONCLUSIONS
  These results suggest that causal attribution of the discrepancy in behavioral phenotypes to the Disc1 L100P mutant mouse line existing among different research groups needs to be cautiously investigated in further study by taking into account the effect(s) of other ENU-induced mutations and/or SNPs from DBA/2 J.
authors.forename: Yosefu
authors.initials: Y
authors.lastname: Arime
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fukumura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Miura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Mekada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshiki
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Gondo
authors.affiliation: Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, 800 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan. kazufuak@dokkyomed.ac.jp.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D059472:Exome / Q000235:genetics; D005260:Female; D007398:Interpersonal Relations; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology
chemical_list: D000697:Central Nervous System Stimulants; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D008694:Methamphetamine