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Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat. Physiol Genomics 2004 Oct 04;19(2):228-32

Date

08/26/2004

Pubmed ID

15328390

DOI

10.1152/physiolgenomics.00126.2004

Scopus ID

2-s2.0-19944386204 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Michalkiewicz M, Michalkiewicz T, Ettinger RA, Rutledge EA, Fuller JM, Moralejo DH, Van Yserloo B, MacMurray AJ, Kwitek AE, Jacob HJ, Lander ES, Lernmark A

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
GTP-Binding Proteins
Genetic Complementation Test
Lung
Lymph Nodes
Lymphopenia
Mutation
RNA, Messenger
Rats
Rats, Inbred BB
Rats, Inbred F344
Rats, Sprague-Dawley
Spleen
T-Lymphocytes
Thymus Gland
Transgenes