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Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program

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Abstract

SHIRPA is a three-stage protocol for the comprehensive assessment of primarily mouse behavior. The first stage consists of high-throughput phenotyping of 33 behavioral observations and 7 metabolic or disease observations. We modified this part of the protocol by integrating new morphologic observations into the initial phenotype assay of behavior and dysmorphology. Behavioral observations assessed by this protocol, now referred to as the “modified-SHIRPA,” are compatible with the original “SHIRPA” protocol. Using modified-SHIRPA, we screened dominant phenotypes of more than 10,000 G1 progeny generated by crossing DBA/2J females with ENU-treated C57BL/6J males. To date, we have obtained 136 hereditary-confirmed mutants that exhibit behavioral and morphologic defects. Some independent mutant lines exhibited similar phenotypes, suggesting that they may represent alleles of the same gene or mutations in the same genetic pathway. They could hold great potential for the unraveling of the molecular mechanisms of certain phenotypes.

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Acknowledgments

The authors thank Dr. Patrick M. Nolan for information about the detailed criteria of the SHIRPA protocol and for helpful advice during the preparation of the article. They thank the technical staff of the Mouse Functional Genomics Research Group of RIKEN GSC for animal care taking and phenotype screening. This study was supported in part by National Bioresources Project of the Ministry of Education, culture, sports, science and technology of Japan.

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Correspondence to Toshihiko Shiroishi.

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Masuya, H., Inoue, M., Wada, Y. et al. Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program. Mamm Genome 16, 829–837 (2005). https://doi.org/10.1007/s00335-005-2430-8

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  • DOI: https://doi.org/10.1007/s00335-005-2430-8

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