PMC:3475480 / 10775-12660
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3475480","sourcedb":"PMC","sourceid":"3475480","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3475480","text":"Discussion\nThis study attempted to validate CASZ1 as a regulator of blood pressure using siRNA in mice. Although Casz1 mRNA levels decreased by 55% in kidney, blood pressure did not change on injection of the siRNA complex into tail veins.\nIt is difficult to conclude that CASZ1 does not control blood pressure, because this study has several limitations. First, Casz1 mRNA levels in kidney were reduced up to 55%; if Casz1 expression had been abolished, we might have detected a significant difference in blood pressure between the case and control groups. Second, it is possible that CASZ1 functions in other tissues besides the kidney in the regulation of blood pressure. The kidney is an essential organ of the urinary system and controls homeostatic functions, such as the regulation of blood pressure, by maintaining salt and water balances. However, the function of CASZ1 in kidney is unknown due to the lack of Casz1 functional studies in kidney. Casz1 is highly expressed in brain, but siRNA nanoparticles do not access the brain due to the blood-brain barrier [15]. Third, human CASZ1 is 87% and 90% identical to mouse Casz1 in the cDNA and polypeptide sequences, respectively [1]. Nevertheless, it is possible that Casz1 function differs between the two species.\nBecause most loci that have been identified by GWASs have several genes nearby, it may be necessary to examine many candidates to identify the functional gene. Knockout and transgenic mice are expensive and time-consuming to generate. In contrast, siRNA injection costs less and is much faster to perform, making siRNA injection suitable for functional validation studies of GWAS results.\nIn summary, we did not observe any significant change in blood pressure in Casz1 siRNA-treated mice, but our study demonstrates the value of in vivo siRNA injection in the functional analysis of candidate genes from GWASs.","divisions":[{"label":"Title","span":{"begin":0,"end":10}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105927-11697206-44845688","span":{"begin":1071,"end":1073},"obj":"11697206"},{"id":"23105927-16631614-44845689","span":{"begin":1188,"end":1189},"obj":"16631614"}],"attributes":[{"subj":"23105927-11697206-44845688","pred":"source","obj":"2_test"},{"subj":"23105927-16631614-44845689","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93c0","default":true}]}]}}