Human Molecular Genetics, 1999, Vol. 8, No. 10 1955-1963
© 1999 Oxford University Press
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Mouse ENU Mutagenesis
Department of Molecular and Human Genetics and 1Howard Hughes Medical Institute,Baylor College of Medicine, One Baylor Plaza, Houston, TX 77096,USA
ABSTRACT
The progress of human genome sequencing is drivinggenetic approaches to define gene function. Strategies such as genetraps and chemical mutagenesis will soon generate a large mutantmouse resource. Point mutations induced by N-ethyl-N-nitrosourea (ENU) provide a unique mutant resourcebecause they: (i) reflect the consequences of single gene changeindependent of position effects; (ii) provide a fine-structure dissectionof protein function; (iii) display a range of mutant effects fromcomplete or partial loss of function to exaggerated function; and(iv) discover gene functions in an unbiased manner. Phenotype-drivenENU screens in the mouse are emphasizing relevance to human clinicaldisease by targeting cardiology, physiology, neurology, immunity,hematopoiesis and mammalian development. Such approaches are extremelypowerful in understanding complex human diseases and traits: thebase-pair changes may accurately model base changes found in humandiseases, and subtle mutant alleles in a standard genetic backgroundprovide the ability to analyze the consequences of compound genotypes.Ongoing mouse ENU mutagenesis experiments are generating a treasuretrove of new mutations to allow an in-depth study of a single gene,a chromosomal region or a biological system.
FOOTNOTES
a Towhom correspondence should be addressed. Tel: +1 713 7985440; Fax: +1 713 798 1489; Email: mjustice{at}bcm.tmc.edu
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