Abstract P124: Blood Pressure Characterization In Btg2 Mutant Rat
| Autor: | Aron M. Geurts, Matthew Hoffman, Eric Jensen, Rebecca Schilling, Michael Grzybowski, Akiko Takizawa, Melinda R. Dwinell |
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| Rok vydání: | 2020 |
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| Zdroj: | Hypertension. 76 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.76.suppl_1.p124 |
| Popis: | Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well established that men and women develop BP impairment in different patterns and a recent emphasis has been placed on identifying mechanisms leading to the differences observed between the sexes in HTN development. The current work reported here builds on an extensive genetic mapping experiment which sought to identify genetic determinants of salt sensitive (SS) HTN using the Dahl SS rat. BTG anti-proliferation factor 2 ( Btg2 ) was previously isolated by our group using congenic breeding experiments which identified it as a female causative SS HTN candidate gene. In the current study, Btg2 was mutated using TALEN targeted gene disruption on the SSBN congenic rat background. The Btg2 mutated rats exhibited impaired BP and proteinuria responses to a high salt diet compared to wild type littermates. Differences in body weight, mutant pup viability, skeletal morphology, and adult nephron density suggest a potential role for Btg2 in developmental signaling pathways. Subsequent cell cycle gene expression assessment provides several additional signaling pathways that Btg2 may function through during salt handling in the kidney. The expression analysis also indicates several upstream targets that can be explored to further isolate therapeutic approaches for SS HTN. |
| Databáze: | OpenAIRE |
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