Mouse Mutagenesis and Disease Models for Neuropsychiatric Disorders

  • Yoichi Gondo
  • Takuya Murata
  • Shigeru Makino
  • Ryutaro Fukumura
  • Yuichi Ishitsuka
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 7)


In this chapter, mutant mouse resources which have been developed by classical genetics as well as by modern large-scale mutagenesis projects are summarized. Various spontaneous and induced mouse mutations have been archived since the rediscovery of Mendel’s genetics in 1900. Moreover, genome-wide, large-scale mutagenesis efforts have recently been expanding the available mutant mouse resources. Forward genetics projects using ENU mutagenesis in the mouse were started in the mid-1990s. The widespread adoption of reverse genetics, using knockouts and conditional mutagenesis based on gene-targeting technology, followed. ENU mutagenesis has now evolved to provide a further resource for reverse genetics, with multiple point mutations in a single gene and this new approach is described. Researchers now have various options to obtain mutant mice: point mutations, transgenic mouse strains, and constitutional or conditional knockout mice. The established mutant strains have already contributed to modeling human diseases by elucidating the underlying molecular mechanisms as well as by providing preclinical applications. Examples of mutant mice, focusing on neurological and behavioral models for human diseases, are reviewed. Human diseases caused by a single gene or a small number of major genes have been well modeled by corresponding mutant mice. Current evidence suggests that quantitative traits based on polygenes are likely to be associated with a range of psychiatric diseases, and these are now coming within the range of modeling by mouse mutagenesis.


ENU Forward genetics Functional genomics Model mouse Mutagenesis Neurological mutation Reverse genetics 



Alzheimer’s disease


Amyloid precursor protein




Central nervous system




d-amino acid oxidase


Episodic ataxia


European Mutant Mouse Archive




European Conditional Mouse Mutagenesis


Forced swim test


Fragile X tremor/ataxia syndrome

G0, G1, G2

Generation-0, Generation-1, Generation-2






Huntington’s disease


High-resolution melting


International Mouse Strain Resource




Knockout mouse mutagenesis project




Latent inhibition


Muscle–eye–brain disease




N-methyl-d-aspartate receptor


North American Conditional Mouse Mutagenesis


Niemann–Pick C disease


Nonsteroidal anti-inflammatory drug


Online Mendelian inheritance in man


Parkinson’s disease


Prepulse inhibition






RIKEN BioResource Center


Spinocerebellar ataxia


TBP-associated factor


TATA-binding protein


TBP-free TAF-containing complex


Temperature gradient capillary electrophoresis



This work is partly supported by Grant-in-Aid for Scientific Research (A) to 21240043 Y. G., for Grants-in-Aid for Young Scientists (B) to 20790196 R. F. and 21700454 S. M. from the Ministry of Education, Science, Sports and Culture, Japan.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Yoichi Gondo
    • 1
  • Takuya Murata
    • 1
  • Shigeru Makino
    • 1
  • Ryutaro Fukumura
    • 1
  • Yuichi Ishitsuka
    • 1
  1. 1.Mutagenesis and Genomics TeamRIKEN BioResource CenterTsukubaJapan

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