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Mouse Mutagenesis and Disease Models for Neuropsychiatric Disorders

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Molecular and Functional Models in Neuropsychiatry

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 7))

Abstract

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 Various spontaneous and induced mouse mutations have been archived since the rediscovery of Mendel’s genetics in 1900.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.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

CD:

2-Hydroxypropyl-b-cyclodextrin

CNS:

Central nervous system

DA:

Dopamine

DAAO:

d-amino acid oxidase

EA:

Episodic ataxia

EMMA:

European Mutant Mouse Archive

ENU:

N-ethyl-N-nitrosourea

EUCOMM:

European Conditional Mouse Mutagenesis

FST:

Forced swim test

FXTAS:

Fragile X tremor/ataxia syndrome

G0, G1, G2:

Generation-0, Generation-1, Generation-2

GAG:

Glycosaminoglycan

GSL:

Glycosphingolipid

HD:

Huntington’s disease

HRM:

High-resolution melting

IMSR:

International Mouse Strain Resource

KO:

Knockout

KOMP:

Knockout mouse mutagenesis project

L100P:

Leu100Pro

LI:

Latent inhibition

MEB:

Muscle–eye–brain disease

MPS:

Mucopolysaccharidosis

NMDAR:

N-methyl-d-aspartate receptor

NorCOMM:

North American Conditional Mouse Mutagenesis

NPC:

Niemann–Pick C disease

NSAID:

Nonsteroidal anti-inflammatory drug

OMIM:

Online Mendelian inheritance in man

PD:

Parkinson’s disease

PPI:

Prepulse inhibition

PS:

Presenilin

Q31L:

Glu31Leu

RIKEN BRC:

RIKEN BioResource Center

SCA:

Spinocerebellar ataxia

TAF:

TBP-associated factor

TBP:

TATA-binding protein

TFTC:

TBP-free TAF-containing complex

TGCE:

Temperature gradient capillary electrophoresis

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Acknowledgment

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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  1. Mutagenesis and Genomics Team, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan

    Yoichi Gondo, Takuya Murata, Shigeru Makino, Ryutaro Fukumura & Yuichi Ishitsuka

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  1. Yoichi Gondo
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  2. Takuya Murata
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  3. Shigeru Makino
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  4. Ryutaro Fukumura
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  5. Yuichi Ishitsuka
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Correspondence to Yoichi Gondo .

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  1. Global Medical Excellence Cluster (GMEC), King's College London, London, SE1 1UL, United Kingdom

    Jim J. Hagan

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Gondo, Y., Murata, T., Makino, S., Fukumura, R., Ishitsuka, Y. (2011). Mouse Mutagenesis and Disease Models for Neuropsychiatric Disorders. In: Hagan, J. (eds) Molecular and Functional Models in Neuropsychiatry. Current Topics in Behavioral Neurosciences, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2010_106

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