Title

Genetics of the BB rat: association of autoimmune disorders (diabetes, insulitis, and thyroiditis) with lymphopenia and major histocompatibility complex class II

UMMS Affiliation

Department of Pathology

Publication Date

12-1-1995

Document Type

Article

Subjects

Animals; Base Sequence; Crosses, Genetic; Diabetes Mellitus, Type 1; Female; *Genes, MHC Class II; Genetic Markers; Lymphopenia; Male; Molecular Sequence Data; Rats; Rats, Inbred BB; Thyroiditis, Autoimmune

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The BB/Wor rat develops spontaneous autoimmune diabetes mellitus and also frequently develops lymphocytic thyroiditis. To clarify the role of T cell lymphopenia and the major histocompatibility complex (MHC) in the development of these autoimmune disorders, we studied back-cross animals between the inbred thyroiditis and diabetes-prone BBNB/Wor subline (MHC RT1.AuBuDuCu) and three nonlymphopenic MHC-congenic rat strains: PVG.RT.1u (RT1.AuBuDuCu), PVG.R8 (RT1.AaBuDuCu), and PVG.R23 (RT1.AuBaDaCav1). We observed that 1) lymphopenia is absolutely required for the development of spontaneous diabetes and insulitis, and is usually associated with the development of thyroiditis; 2) the MHC region to the right of the class I RT1.A locus is strongly correlated with diabetes and insulitis; and 3) this region is also significantly associated with the development of thyroiditis, but the susceptibility of certain MHC class II alleles (u and a) for disease development is distinct for insulitis and thyroiditis. Furthermore, no recombination was observed between lymphopenia (lyp) and the neuropeptide Y (Npy) gene polymorphism, which confirmed that lyp maps very close to Npy. The present data suggest that spontaneous insulitis and thyroiditis in the BB/Wor rat develop through common immune defects involving T cell lymphopenia, but do not always segregate together due to disease-specific interactions with the MHC class II-linked genes.

Rights and Permissions

Citation: Endocrinology. 1995 Dec;136(12):5731-5.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Endocrinology

PubMed ID

7588330