Differential expression of p95vav in primary lymphoid tissue of BB rats congenic for the lymphopenia gene.
Lyp controls lymphopenia and T-cell mediated autoimmune diabetes in the BioBreeding (BB) rat possibly by interacting with T-cell maturation in the thymus. The protooncogene vav (p95) is involved in T-cell activation and in the intrathymic selection of developing T cells. We have previously reported increased production of IFN-gamma of self reactive thymocytes in the thymus medulla of Lyp/Lyp BB rats. Lymphopenia and diabetes may therefore be linked to an increase in thymocyte activation leading to a bias in thymocyte development. The purpose of this study was therefore to investigate whether the expression of p95"a" in primary lymphoid tissues from congenic Lyp/Lyp, Lyp/+ and +/+ BB rats was correlated to the Lyp genotype using in situ hybridization and reverse transcription (RT)-PCR. It was found that the expression of vav mRNA in the thymus was increased in Lyp/Lyp compared to Lyp/+ and +/+ rats (p < 0.05). Western blot analysis revealed that the amount of p95 vav protein in Lyp/Lyp thymus was also increased. The results show that vav expression correlates with the lymphopenia phenotype and diabetes development in congenic Lyp/Lyp BB rats. An increase in the availability of p95vav during the development and activation of thymocytes in Lyp/Lyp BB rats may therefore contribute to the generation of islet autoreactivity, lymphopenia or both.
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Robert H. Williams Laboratory, Department of Medicine, University of Washington, Seattle 98195, USA. sbieg@u.washington.edu
D000818:Animals; D020296:Animals, Congenic; D015153:Blotting, Western / Q000662:veterinary; D003124:Colorimetry / Q000662:veterinary; D017931:DNA Primers / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000662:veterinary; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D051567:Proto-Oncogene Proteins c-vav; D012313:RNA / Q000737:chemistry; D051381:Rats; D011913:Rats, Inbred BB; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000737:chemistry / Q000276:immunology
D017931:DNA Primers; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496620:Vav1 protein, rat; D012313:RNA