These centers use N-ethyl-N-nitrosourea (ENU) to create mutations in the mouse genome and then screen the resulting mutants for neurological phenotypes. ENU is an ethylating agent that is both mutagenic and cytotoxic in mouse spermatogonial stem cells1. ENU is particularly valuable for inducing allelic series of mutations because it causes primarily base-pair substitutions2, resulting in a wide range of mutation outcomes. Importantly, of the 38,000 mutations in about 1,500 genes that cause aberrant phenotypes in humans, about 70% of these are of the single-base pair variety (http://archive.uwcm.ac.uk/uwcm/mg/docs/hahaha.html), and so it would appear that the ENU-based approach in mice mimics human genetic disease.
Producing mutant mice at the 'industrial' level brings considerable challenges in laboratory information management systems. It requires a database architecture that is flexible and scalable with reliable and secure data storage, and that allows acquisition of data from multiple locations. It should permit tracking of mice individually or collectively as families, and should allow the user to create automated reports and use statistical analysis tools. Effective sharing of data and information about mice and their phenotypes requires the use of standardized data exchange formats, the use of existing community databases and resources, and the development of common vocabularies for new types of data. To address these issues, the three NIH-funded neuroscience mutagenesis centers have formed a virtual distribution center (www.neuromice.org), which allows researchers to learn about and acquire mutant mice of interest. The website uses a standardized XML data exchange format; each mouse file includes a description of the mutant mouse, heritability and mapping status information, distribution notes and links to the web page of the center from which the mutant was derived.
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