Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat.
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.
Department of Physiology, Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-0509, USA. mmichalk@mcw.edu
Mieczyslaw
M
Michalkiewicz
Teresa
T
Michalkiewicz
Ruth A
RA
Ettinger
Elizabeth A
EA
Rutledge
Jessica M
JM
Fuller
Daniel H
DH
Moralejo
Brian
B
Van Yserloo
Armand J
AJ
MacMurray
Anne E
AE
Kwitek
Howard J
HJ
Jacob
Eric S
ES
Lander
Ake
A
Lernmark
D000818:Animals; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005816:Genetic Complementation Test; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000737:chemistry / Q000473:pathology; D019076:Transgenes / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D019204:GTP-Binding Proteins; C494977:Gimap5 protein, rat