Evaluation of the role of fatty acid-binding protein 7 in controlling schizophrenia-relevant phenotypes using newly established knockout mice

Chie Shimamoto-Mitsuyama, Tetsuo Ohnishi, Shabeesh Balan, Hisako Ohba, Akiko Watanabe, Motoko Maekawa, Yasuko Hisano, Yoshimi Iwayama, Yuji Owada, Takeo Yoshikawa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Dampened prepulse inhibition (PPI) is a consistent observation in psychiatric disorders, including schizophrenia and qualifies as a robust endophenotype for genetic evaluation. Using high PPI C57BL/6NCrlCrlj (B6Nj) and low PPI C3H/HeNCrlCrlj (C3HNj) inbred mouse strains, we have previously reported a quantitative trait locus (QTL) for PPI at chromosome 10 and identified Fabp7 as a candidate gene for regulating PPI and schizophrenia pathogenesis using Fabp7-deficient mice (B6.Cg-Fabp7 KO). Here, considering a possibility of carryover of residual genetic materials from embryonic stem (ES) cells used in generating knockout (KO) mice, we set out to re-address the genotype-phenotype correlation in a uniform genetic background. By generating a new Fabp7 KO mouse model in C57BL/6NCrl (B6N) background using the CRISPR-Cas9 nickase system, we evaluated the impact of Fabp7 ablation on schizophrenia-related behavioral phenotypes. To our surprise, we found no significant differences in PPI or any of the schizophrenia-related behavioral scores, as observed in our previous B6.Cg-Fabp7 KO mice. We identified several C3H/He mouse strain-specific alleles within the interval of chromosome 10-QTL, which are shared with 129/Sv mouse strains. These alleles, derived from 129/Sv ES cells, were retained in the B6.Cg-Fabp7 KO, despite multiple backcrossing and are thought to be responsible for the dampened PPI. In summary, our study demonstrates a precise genotype-phenotype relation for Fabp7 loss-of-function in a uniform B6N background, and raises the necessity of further analysis of the effects of genomic variants flanking the Fabp7 interval on phenotypes.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalSchizophrenia Research
Volume217
DOIs
Publication statusPublished - 2020 Mar
Externally publishedYes

Keywords

  • Cadherin related 23
  • Fatty acid-binding protein 7
  • Mouse behaviors
  • Prepulse inhibition
  • Psychiatric disorder

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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