Journal article
Diabetes-prone and diabetes-resistant BB rats share a common major diabetes susceptibility locus, iddm4: additional evidence for a "universal autoimmunity locus" on rat chromosome 4
Diabetes (New York, N.Y.), Vol.48(11), pp.2138-2144
Nov 1999
PMID: 10535446
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diabetes-prone (DP) BB rats develop autoimmune type 1 diabetes spontaneously. At least five loci are linked to disease expression: the major histocompatibility complex (iddm2), two susceptibility loci (iddm4, iddm5), and, possibly, a resistance locus (iddm3). Spontaneous disease also requires homozygosity for lyp/iddm1, which causes lymphopenia. It has not been determined whether lyp/iddm1 is required for predisposition to diabetes autoimmunity in addition to being required for its spontaneous expression. We analyzed backcross rats segregating for diabetes but not lymphopenia using Wistar-Furth (WF) and diabetes-resistant (DR) BB animals. The latter are nonlymphopenic (lyp+/+) and develop diabetes only in response to immunological perturbants. Treatment of (DR-BB x WF)F1 x WF animals (all lyp+/+) using a standard induction protocol caused type 1 diabetes in 58% of progeny. Expression of type 1 diabetes was strongly linked to iddm4. The results suggest that lyp/iddm1 does not determine the predisposition to autoimmunity in BB rats and that iddm4 is a major diabetogenic locus in both DP- and DR-BB animals. The iddm4 gene maps to a region containing several major autoimmunity loci, including aia2, aia3, and cia3. We propose that BB rat diabetes requires 1) class II RT1u (iddm2) for susceptibility, 2) additional loci for disease initiation and progression in response to perturbants, and 3) lyp for spontaneous disease.
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Details
- Title
- Diabetes-prone and diabetes-resistant BB rats share a common major diabetes susceptibility locus, iddm4: additional evidence for a "universal autoimmunity locus" on rat chromosome 4
- Creators
- A M Martin - Department of Microbiology and Immunology, Medical College of Pennsylvania Hahnemann University, Philadelphia, USAM N MaxsonJ LeifJ P MordesD L GreinerE P Blankenhorn
- Publication Details
- Diabetes (New York, N.Y.), Vol.48(11), pp.2138-2144
- Publisher
- American Diabetes Association; United States
- Grant note
- DK-36024 / NIDDK NIH HHS DK-49106 / NIDDK NIH HHS DK-41235 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Identifiers
- 991014878341004721
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- Endocrinology & Metabolism