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Physiol Genomics DOI:10.1152/physiolgenomics.00126.2004

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

Publication TypeJournal Article
Year of Publication2004
AuthorsMichalkiewicz, M, Michalkiewicz, T, Ettinger, RA, Rutledge, EA, Fuller, JM, Moralejo, DH, Van Yserloo, B, MacMurray, AJ, Kwitek, AE, Jacob, HJ, Lander, ES, Lernmark, A
JournalPhysiol Genomics
Date Published2004 Oct 04
KeywordsAnimals, Genetic Complementation Test, GTP-Binding Proteins, Lung, Lymph Nodes, Lymphopenia, Mutation, Rats, Rats, Inbred BB, Rats, Inbred F344, Rats, Sprague-Dawley, RNA, Messenger, Spleen, T-Lymphocytes, Thymus Gland, Transgenes

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.


Alternate JournalPhysiol. Genomics
PubMed ID15328390
Grant ListAI-42380 / AI / NIAID NIH HHS / United States
HL-57921 / HL / NHLBI NIH HHS / United States