Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Asthma / genetics*
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Asthma / immunology
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Bronchial Hyperreactivity / genetics*
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Bronchial Hyperreactivity / immunology
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Cells, Cultured
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Chromosome Mapping
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Chromosomes, Human, Pair 5
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Cloning, Molecular
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Genetic Predisposition to Disease
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Hepatitis A Virus Cellular Receptor 1
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Hepatitis A Virus Cellular Receptor 2
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Humans
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Interleukin-13 / biosynthesis
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Interleukin-4 / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Proteins / genetics*
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Membrane Proteins / physiology
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Mice
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Mice, Inbred DBA
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Molecular Sequence Data
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Multigene Family
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Polymorphism, Genetic
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Receptors, Virus / genetics
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Sequence Homology, Amino Acid
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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HAVCR1 protein, human
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Havcr1 protein, mouse
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Havcr2 protein, mouse
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Hepatitis A Virus Cellular Receptor 1
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Hepatitis A Virus Cellular Receptor 2
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Interleukin-13
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Membrane Glycoproteins
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Membrane Proteins
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Receptors, Virus
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Timd2 protein, mouse
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Interleukin-4
Associated data
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GENBANK/AF399827
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GENBANK/AF399828
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GENBANK/AF399829
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GENBANK/AF399830
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GENBANK/AF399831