RGD Reference Report - Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat. - Rat Genome Database

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Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat.

Authors: Dhande, Isha S  Kneedler, Sterling C  Zhu, Yaming  Joshi, Aniket S  Hicks, M John  Wenderfer, Scott E  Braun, Michael C  Doris, Peter A 
Citation: Dhande IS, etal., Genes Immun. 2020 May;21(3):182-192. doi: 10.1038/s41435-020-0097-5. Epub 2020 Apr 17.
RGD ID: 149735373
Pubmed: (View Article at PubMed) PMID:32300198
DOI: Full-text: DOI:10.1038/s41435-020-0097-5

Similar to humans, the risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study, we show the involvement of genetic variation affecting the store-operated calcium signaling gene, Stim1, in the pathogenesis of stroke in SHR. Stim1 is a key lymphocyte activation signaling molecule and contains functional variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which Stim1 was substituted with the corresponding genomic segment from SHR-B2. Compared with SHR-A3 rats, Stim1 congenic SHR-A3 (SHR-A3(Stim1-B2)) have reduced cerebrovascular disease in response to salt loading including lower neurological deficit scores and cerebral edema. Microbleeds and major hemorrhages occurred in over half of SHR-A3 rats. These lesions were absent in SHR-A3(Stim1-B2) rats. Loss of Stim1 function in mice and humans is associated with antibody-mediated autoimmunity due to defects in T lymphocyte helper function to B cells. We investigated autoantibody formation using a high-density protein array to detect the presence of IgG and IgM autoantibodies in SHR-A3. Autoantibodies to key cerebrovascular stress proteins were detected that were reduced in the congenic line.

Disease Annotations    
Stroke  (IAGP)

Objects Annotated

Objects referenced in this article
Marker rs106374972 rs106374972 Rattus norvegicus
Marker rs106170276 rs106170276 Rattus norvegicus
Marker rs198445122 rs198445122 Rattus norvegicus
Marker rs197197017 rs197197017 Rattus norvegicus

Additional Information