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dc.contributor.authorAwata, Takuya
dc.contributor.authorGuberski, Dennis L.
dc.contributor.authorLike, Arthur A.
dc.date2022-08-11T08:10:02.000
dc.date.accessioned2022-08-23T16:52:56Z
dc.date.available2022-08-23T16:52:56Z
dc.date.issued1995-12-01
dc.date.submitted2008-07-09
dc.identifier.citation<p>Endocrinology. 1995 Dec;136(12):5731-5.</p>
dc.identifier.issn0013-7227 (Print)
dc.identifier.pmid7588330
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42158
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=7588330&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1210/en.136.12.5731
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCrosses, Genetic
dc.subjectDiabetes Mellitus, Type 1
dc.subjectFemale
dc.subject*Genes, MHC Class II
dc.subjectGenetic Markers
dc.subjectLymphopenia
dc.subjectMale
dc.subjectMolecular Sequence Data
dc.subjectRats
dc.subjectRats, Inbred BB
dc.subjectThyroiditis, Autoimmune
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleGenetics of the BB rat: association of autoimmune disorders (diabetes, insulitis, and thyroiditis) with lymphopenia and major histocompatibility complex class II
dc.typeArticle
dc.source.journaltitleEndocrinology
dc.source.volume136
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/530
dc.identifier.contextkey545012
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/530
dc.contributor.departmentDepartment of Pathology
dc.source.pages5731-5


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