ENU Mutagenesis Screening for Dominant Behavioral Mutations Based on Normal Control Data Obtained in Home-Cage Activity, Open-Field, and Passive Avoidance Tests

Yumiko WADA; Tamio FURUSE; Ikuko YAMADA; Hiroshi MASUYA; Tomoko KUSHIDA; Yoko SHIBUKAWA; Yuji NAKAI; Kimio KOBAYASHI; Hideki KANEDA; Yoichi GONDO; Tetsuo NODA; Toshihiko SHIROISHI; Shigeharu WAKANA

doi:10.1538/expanim.59.495

Original

ENU Mutagenesis Screening for Dominant Behavioral Mutations Based on Normal Control Data Obtained in Home-Cage Activity, Open-Field, and Passive Avoidance Tests

Yumiko WADA, Tamio FURUSE, Ikuko YAMADA, Hiroshi MASUYA, Tomoko KUSHIDA, Yoko SHIBUKAWA, Yuji NAKAI, Kimio KOBAYASHI, Hideki KANEDA, Yoichi GONDO, Tetsuo NODA, Toshihiko SHIROISHI, Shigeharu WAKANA

Author information

Yumiko WADA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Department of Humanities, Kyusyu Lutheran College
Tamio FURUSE
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Ikuko YAMADA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Hiroshi MASUYA
Technology and Development Unit for Knowledge Base of Mouse Phenotype, RIKEN BioResource Center
Tomoko KUSHIDA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Yoko SHIBUKAWA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Yuji NAKAI
Mutagenesis and Genomics Team, RIKEN BioResource Center
Kimio KOBAYASHI
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Hideki KANEDA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center
Yoichi GONDO
Mutagenesis and Genomics Team, RIKEN BioResource Center
Tetsuo NODA
Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center
Toshihiko SHIROISHI
Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics
Shigeharu WAKANA
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center

Keywords: behavior, ENU, mice, mutagenesis, mutants

JOURNAL FREE ACCESS

2010 Volume 59 Issue 4 Pages 495-510

DOI https://doi.org/10.1538/expanim.59.495

Details

Abstract

To establish the cutoff values for screening ENU-induced behavioral mutations, normal variations in mouse behavioral data were examined in home-cage activity (HA), open-field (OF), and passive-avoidance (PA) tests. We defined the normal range as one that included more than 95% of the normal control values. The cutoffs were defined to identify outliers yielding values that deviated from the normal by less than 5% for C57BL/6J, DBA/2J, DBF₁, and N₂ (DXDB) progenies. Cutoff values for G1-phenodeviant (DBF₁) identification were defined based on values over ± 3.0 SD from the mean of DBF₁ for all parameters assessed in the HA and OF tests. For the PA test, the cutoff values were defined based on whether the mice met the learning criterion during the 2nd (at a shock intensity of 0.3 mA) or the 3rd (at a shock intensity of 0.15 mA) retention test. For several parameters, the lower outliers were undetectable as the calculated cutoffs were negative values. Based on the cutoff criteria, we identified 275 behavioral phenodeviants among 2,646 G1 progeny. Of these, 64 were crossed with wild-type DBA/2J individuals, and the phenotype transmission was examined in the G2 progeny using the cutoffs defined for N₂ mice. In the G2 mice, we identified 15 novel dominant mutants exhibiting behavioral abnormalities, including hyperactivity in the HA or OF tests, hypoactivity in the OF test, and PA deficits. Genetic and detailed behavioral analysis of these ENU-induced mutants will provide novel insights into the molecular mechanisms underlying behavior.

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