Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1, on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Comparative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes.
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PMID:A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat. 932 65

BB-Diabetes Prone (BB-DP) rats, a model for endocrine autoimmune diseases, are severely lymphopenic, especially lacking ART2+ regulatory T cells. BB-Diabetes Resistant (DR) rats are not lymphopenic and do not develop autoimmunity. BB-DP and BB-DR rats only differ at the lymphopenia (lyp) gene (iddm2) on chromosome 4. Since BB-DP rats also show aberrancies in the differentiation of dendritic cells (DC) from bone-marrow precursors, we tested the hypothesis that F344 rats congenic for a BB-DP chromosome 4 region (42.5-93.6Mb; including the lyp gene, but also iddm4) display an in vitro DC differentiation different from normal F344 rats. Here we show that the 42.5-93.6Mb BB-DP chromosome 4 region is linked to an increased DC precursor apoptosis, a low MHC class II expression, a reduced IL-10 production and a reduced T cell stimulatory capacity of DC. From our previous report on DC differentiation defects in BB rats (only differing in iddm2) and the present report, we deduce that the abnormal apoptosis and low MHC class II expression is linked to iddm2. The reduced T cell stimulatory capacity is linked to other genes on chromosome 4 (candidate gene: iddm4). The reduced IL-10 production has a complex linkage pattern.
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PMID:Aberrancies in the differentiation and maturation of dendritic cells from bone-marrow precursors are linked to various genes on chromosome 4 and other chromosomes of the BB-DP rat. 1602 26