. "metabolic syndrome; spontaneously hypertensive rat; transgenic; gene; mutation; orthologous human loci"@en . " transgenic" . . "2014-03-06+01:00"^^ . . . "http://www.isvav.cz/projectDetail.do?rowId=LH12061"^^ . "2015-12-31+01:00"^^ . "Hlavn\u00EDm c\u00EDlem projektu je odhalen\u00ED molekul\u00E1rn\u00ED podstaty hypertenze a metabolick\u00FDch poruch u kmene SHR a n\u00E1sledn\u00E9 odhalen\u00ED \u00FAlohy lidsk\u00FDch ortologn\u00EDch lokus\u016F. C\u00EDl \u010D. 1 U vybran\u00FDch kandid\u00E1tn\u00EDch gen\u016F zjist\u00EDme vliv mutac\u00ED na hladiny mRNA a protein\u016F pomoc\u00ED real time PCR a Western blotingu v ledvin\u011B a dal\u0161\u00EDch relevantn\u00EDch tk\u00E1n\u00EDch u SHR, BN a SHR.BN-kongenn\u00EDch kmen\u016F. Pot\u00E9 co potvrd\u00EDme, \u017Ee mutace vybran\u00FDch gen\u016F jsou spojeny se ztr\u00E1tou jejich funkce, provedeme in vivo funk\u010Dn\u00ED anal\u00FDzy s vyu\u017Eit\u00EDm transgenn\u00ED komplementa\u010Dn\u00ED strategie: vytvo\u0159\u00EDme SHR transgenn\u00ED linie, kter\u00E9 budou exprimovat norm\u00E1ln\u00ED (nezmutovanou) cDNA pod kontrolou tk\u00E1\u0148ov\u011B specifick\u00FDch promotor\u016F. C\u00EDl \u010D. 2 Transgenn\u00ED linie exprimuj\u00EDc\u00ED norm\u00E1ln\u00ED varianty vybran\u00FDch gen\u016F budou testov\u00E1ny v hemodynamick\u00FDch a metabolick\u00FDch parametrech s c\u00EDlem odhalit fenotypick\u00E9 \u00FA\u010Dinky (transgenn\u00ED komplementaci) spojen\u00E9 s expres\u00ED transgen\u016F. C\u00EDl \u010D. 3 Odhalen\u00ED funk\u010Dn\u00ED v\u00FDznamnosti ortologn\u00EDch lokus\u016F u lid\u00ED pomoc\u00ED in silico anal\u00FDz s vyu\u017Eit\u00EDm ve\u0159ejn\u011B dostupn\u00FDch dat." . "6"^^ . . "LH12061" . . "6"^^ . . . "2015-02-16+01:00"^^ . . "Identification of molecular and functional basis of pathophysiological phenotypes in the spontaneously hypertensive rat"@en . "0"^^ . . . "metabolic syndrome" . . . "1"^^ . . . "0"^^ . " mutation" . " gene" . "To identify at the molecular level gene variants that are responsible for variability in complex hemodynamic and metabolic traits. Specific aim 1. We will assess the impact of selected mutant genes on mRNA and protein levels by real time PCR and Western blot studies of kidney and other relevant tissues in the SHR and BN progenitor strains and in SHR.BN congenic strains. After confirming the loss of function, we will test these variants by in vivo functional studies using a transgenic rescue strategy. We will derive SHR transgenic lines that will express wild type cDNA under tissue specific promoters. Specific aim 2. Transgenic SHR lines expressing wild type variants of mutated genes will be tested in metabolic and hemodynamic parameters to detect phenotypic effects associated with the transgene expression. Specific aim 3. Identification of functional significance of human ortologous genes by in silico analyses using publicly available databases."@en . "Odhalen\u00ED molekul\u00E1rn\u00ED a funk\u010Dn\u00ED podstaty patofyziologick\u00FDch fenotyp\u016F u spont\u00E1nn\u011B hypertenzn\u00EDch potkan\u016F" . . "2012-03-01+01:00"^^ . . . . " spontaneously hypertensive rat" .