Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family.
To simplify the analysis of asthma susceptibility genes located at human chromosome 5q23-35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait encoded by T cell and Airway Phenotype Regulator (Tapr). Tapr is genetically distinct from known cytokine genes and controls the development of airway hyperreactivity and T cell production of interleukin 4 (IL-4) and IL-13. Positional cloning identified a gene family that encodes T cell membrane proteins (TIMs); major sequence variants of this gene family (Tim) completely cosegregated with Tapr. The human homolog of TIM-1 is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy.
McIntire
J J
JJ
Division of Immunology and Allergy, Department of Pediatrics and the Howard Hughes Institute, Stanford University, Stanford, CA 94305-5208, USA.
Umetsu
S E
SE
Akbari
O
O
Potter
M
M
Kuchroo
V K
VK
Barsh
G S
GS
Freeman
G J
GJ
Umetsu
D T
DT
DeKruyff
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D020022:Genetic Predisposition to Disease; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D005810:Multigene Family; D011110:Polymorphism, Genetic; D011991:Receptors, Virus / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
C491143:HAVCR1 protein, human; C442240:Havcr1 protein, mouse; C442241:Havcr2 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C442242:Timd2 protein, mouse; D015847:Interleukin-4