|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||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|
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.