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Physiol. Genomics 19: 228-232, 2004. First published August 24, 2004; doi:10.1152/physiolgenomics.00126.2004
1094-8341/04 $5.00
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Received 26 May 2004; accepted in final form 4 August 2004.
Physiological Genomics 19:228-232 (2004)
1094-8341/04 $5.00 © 2004 American Physiological Society

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Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat

Mieczyslaw Michalkiewicz1, Teresa Michalkiewicz1, Ruth A. Ettinger2, Elizabeth A. Rutledge2, Jessica M. Fuller2, Daniel H. Moralejo2, Brian Van Yserloo2, Armand J. MacMurray2, Anne E. Kwitek1, Howard J. Jacob1, Eric S. Lander3,4,5,6 and Åke Lernmark2

1 Department of Physiology, Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
2 Department of Medicine, University of Washington, Seattle, Washington 98195
3 Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02138
4 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
5 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115
6 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02141

ABSTRACT

A single point mutation in a novel immune-associated nucleotide gene 5 (Ian5) coincides with severe T cell lymphopenia in BB rats. We used a transgenic rescue approach in lymphopenic BB-derived congenic F344.lyp/lyp rats to determine whether this mutation is responsible for lymphopenia and to establish the functional importance of this novel gene. A 150-kb P1 artificial chromosome (PAC) transgene harboring a wild-type allele of the rat Ian5 gene restored Ian5 transcript and protein levels, completely rescuing the T cell lymphopenia in the F344.lyp/lyp rats. This successful complementation provides direct functional evidence that the Ian5 gene product is essential for maintaining normal T cell levels. It also demonstrates that transgenic rescue in the rat is a practical and definitive method for revealing the function of a novel gene.

diabetes; lymphopenia; apoptosis




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