Abstract:
:Using CRISPR-Cas9 technology, we created a 5-HT7 receptor global knockout (KO) rat, on a Sprague-Dawley background, for use in cardiovascular physiology studies focused on blood pressure regulation. A stable line carrying indels in exons 1 and 2 of the rat Htr7 locus was established and validated. Surprisingly, 5-HT7 receptor mRNA was still present in the KO rat. However, extensive cDNA and genomic sequencing of KO tissues confirmed an 11 bp deletion in exon 1 and 4 bp deletion in exon 2. The exon 1 deletion resulted in a frameshifted mRNA sequence coding for a nonfunctional protein. While the Htr1B locus was a potential off-target for the guide RNAs designed for exon 2 of Htr7, there were no off-target sequence changes at this locus in the originating founder. When the F2 generation of KO was compared with wild-type (WT) counterparts, neither the male nor female KO rats were different in body size, fat weights, or mass of organs (kidney, heart, and brain) important to blood pressure. Females were smaller in mass than their counterpart males. Clinical measures of plasma from nonfasted rats revealed largely similar values, comparing WT and KO, of glucose, blood urea nitrogen, creatinine, phosphate, calcium, and albumin to name a few. Loss of a functional 5-HT7 receptor was validated by the complete loss of relaxation to the 5-HT1/7 receptor agonist 5-carboxamidotryptamine in the isolated abdominal vena cava. This newly created 5-HT7 receptor KO rat will be of use to investigate the importance of the 5-HT7 receptor in blood pressure regulation.
journal_name
Physiol Genomicsjournal_title
Physiological genomicsauthors
Demireva EY,Xie H,Flood ED,Thompson JM,Seitz BM,Watts SWdoi
10.1152/physiolgenomics.00030.2019subject
Has Abstractpub_date
2019-07-01 00:00:00pages
290-301issue
7eissn
1094-8341issn
1531-2267journal_volume
51pub_type
杂志文章abstract::Previous studies have indicated that hemorrhage may predispose the lung to respiratory distress syndrome. Gene expression profiling with oligonucleotide microarrays was used to evaluate the genetic responses of the lung to hemorrhage. Conscious rats, chronically instrumented with a catheter and telemetry device to rec...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00075.2005
更新日期:2005-11-17 00:00:00
abstract::Disordered angiogenesis is implicated in pulmonary vascular remodeling secondary to congenital heart diseases (CHD). However, the underlying genes are not well delineated. We showed previously that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an "angiogenesis burst" between 1 and 4 wk of ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00135.2010
更新日期:2011-01-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disorder with immune-complex deposition that affects multiple organs. Previous studies have suggested the involvement of oxidative stress and apoptosis in SLE, but no clear link to etiology has been established. Here we show that mice deficient in a transcription fac...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00209.2003
更新日期:2004-08-11 00:00:00
abstract::The involvement of heat-inducible genes, including the heat-shock genes, in the acute response to temperature stress is well established. However, their importance in genetic adaptation to long-term temperature stress is less clear. Here we use high-density arrays to examine changes in expression for 35 heat-inducible...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00034.2002
更新日期:2003-06-24 00:00:00
abstract::Preeclampsia (PE) is a devastating adverse outcome of pregnancy. Characterized by maternal hypertension, PE, when left untreated, can result in death of both mother and baby. The cause of PE remains unknown, and there is no way to predict which women will develop PE during pregnancy. The only known treatment is delive...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00102.2018
更新日期:2019-03-01 00:00:00
abstract::The gastric entero-chromaffin-like (ECL) cell plays a key regulatory role in peripheral regulation of acid secretion due to the release of histamine that stimulates acid secretion by the parietal cell. Studies in intact animals, gastric glands, and isolated cells after short-term culture have shown expression of stimu...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00271.2005
更新日期:2006-03-13 00:00:00
abstract::Physiological, morphological, and transcriptional alterations elicited by ethynyl estradiol in the uteri of Sprague-Dawley rats and C57BL/6 mice were assessed using comparable study designs, microarray platforms, and analysis methods to identify conserved estrogen signaling networks. Comparative analysis identified 15...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00175.2005
更新日期:2005-11-17 00:00:00
abstract::Cultured shrimp are continuously exposed to variable environmental conditions that have been associated with stress and subsequent outbreaks of disease. To investigate the effect of environmental stress on Penaeus monodon gene expression, a 3,853 random cDNA microarray chip was generated with clones originating from s...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00068.2007
更新日期:2007-09-19 00:00:00
abstract::Branchial ammonia transport in freshwater teleosts is not well understood. Most studies conclude that NH(3) diffuses out of the gill and becomes protonated to NH(4)(+) in an acidified gill boundary layer. Rhesus (Rh) proteins are new members of the ammonia transporter superfamily and rainbow trout possess genes encodi...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00061.2007
更新日期:2007-11-14 00:00:00
abstract::We previously reported that markers on rat chromosome 1 are genetically linked to blood pressure in an F(2) population derived from Dahl salt hypertension-sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one blood pressure quantitative trait locus (QTL) on chromosome 1, an initial congenic ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.1999.1.3.119
更新日期:1999-11-11 00:00:00
abstract::Model organisms have been used over a century to understand basic, conserved biological processes. The study of these experimental systems began with genetics and development, moved into molecular and cellular biology, and most recently propelled into functional genomics and proteomics. The goal of this review is simp...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00075.2002
更新日期:2003-03-18 00:00:00
abstract::Mechanical ventilation is a life-saving intervention in patients with respiratory failure. However, human and animal studies have demonstrated that mechanical ventilation using large tidal volumes (>or=12 ml/kg) induces a potent inflammatory response and can cause acute lung injury. We hypothesized that mechanical ven...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00027.2009
更新日期:2009-05-13 00:00:00
abstract::Resiquimod is a compound belonging to the imidazoquinoline family of compounds known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. The aim of the present study was to elucidate the molecular processes tha...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00057.2009
更新日期:2009-08-07 00:00:00
abstract::Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It is essential that the tests designed provide reliable measures of the process under investigation but most importantly that these are reproducible across both time and la...
journal_title:Physiological genomics
pub_type: 杂志文章,多中心研究
doi:10.1152/physiolgenomics.90207.2008
更新日期:2008-08-15 00:00:00
abstract::Genetic analysis of polygenic traits in rats and mice has been very useful for finding the approximate chromosomal locations of the genes causing quantitative phenotypic variation, so-called quantitative trait loci (QTL). Further localization of the causative genes and their ultimate identification has, however, prove...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00136.2011
更新日期:2012-02-01 00:00:00
abstract::Leptin is known as a cytokine mostly produced by fat cells and implicated in regulation of energy metabolism and food intake but has also been shown to be involved in many physiological mechanisms such as tissue metabolism and cell differentiation and proliferation. In particular, leptin influences the development of ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00020.2013
更新日期:2013-08-01 00:00:00
abstract::Vasopressin is a peptide hormone that regulates renal water excretion in part through its actions on the collecting duct. The regulation occurs in part via control of transcription of genes coding for the water channels aquaporin-2 (Aqp2) and aquaporin-3 (Aqp3). To identify transcription factors expressed in collectin...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00148.2009
更新日期:2010-02-04 00:00:00
abstract::Exercise as well as hypoxia cause an increase in angiogenesis, changes in mitochondrial density and alterations in metabolism, but it is still under debate whether the hypoxia inducible factor (HIF) is active during both situations. In this study gene expression analysis of zebrafish larvae that were raised under norm...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00250.2010
更新日期:2011-05-13 00:00:00
abstract::Hypoxia is an important ecological, evolutionary, and biomedical stressor. While physiological acclimatization of mammals to hypoxia is well studied, the variation in gene expression that underlies acclimatization is not well studied. We acclimatized inbred mice for 32 days to hypoxic conditions that simulated altitud...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00075.2009
更新日期:2010-05-01 00:00:00
abstract::The relative importance of regulatory versus structural evolution for the evolution of different biological systems is a subject of controversy. The primacy of regulatory evolution in the diversification of morphological traits has been promoted by many evolutionary developmental biologists. For physiological traits, ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00159.2007
更新日期:2008-11-12 00:00:00
abstract::Cystic fibrosis (CF) lung disease severity is influenced by unknown genetic factors apart from the disease causative gene, cystic fibrosis transmembrane conductance regulator (CFTR). Previous studies have shown the C57BL/6J congenic Cftr(-/-) (B6 CF) mouse to develop a fibrotic lung disease compared with both CF mice ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00208.2005
更新日期:2006-04-13 00:00:00
abstract::Preeclampsia is a progressive hypertensive disorder of pregnancy affecting 2-8% of pregnancies globally. Preexisting chronic hypertension is a major risk factor associated with developing preeclampsia, and growing evidence suggests a role for the gut microbiome in the development of preeclampsia. However, neither alte...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00121.2020
更新日期:2021-01-25 00:00:00
abstract::The mammary gland undergoes extensive remodeling between the beginning of pregnancy and lactation; this involves cellular processes including cell proliferation, differentiation, and apoptosis, all of which are under the control of numerous regulators. To unravel the role played by miRNA, we describe here 47 new ovine...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00091.2012
更新日期:2013-02-15 00:00:00
abstract::Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of th...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00222.2003
更新日期:2004-07-08 00:00:00
abstract::Slc22 family organic anion and cation transporters (OATs, OCTs, and OCTNs) are transmembrane proteins expressed predominantly in kidney and liver. These proteins mediate the uptake or excretion of numerous physiologically (and pharmacologically) important compounds, and accordingly have been the focus of intensive stu...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00014.2004
更新日期:2004-06-17 00:00:00
abstract::Higher fat and lower carbohydrate and amino acid oxidation are observed in women compared with men during endurance exercise. We hypothesized that the observed sex difference is due to estrogen and that menstrual cycle phase or supplementation of men with 17beta-estradiol (E(2)) would coordinately influence the mRNA c...
journal_title:Physiological genomics
pub_type: 杂志文章,随机对照试验
doi:10.1152/physiolgenomics.00115.2009
更新日期:2009-12-30 00:00:00
abstract::Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP)...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00095.2007
更新日期:2008-03-14 00:00:00
abstract::The genetic basis of susceptibility to pulmonary fibrosis is largely unknown. Initially, in this study, loci regulating the response of bleomycin-induced pulmonary fibrosis were mapped using a set of recombinant congenic strains bred from pulmonary fibrosis-resistant A/J and susceptible C57BL/6J (B6) mice. Linkage was...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00095.2005
更新日期:2005-09-21 00:00:00
abstract::Intrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance runnin...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00118.2015
更新日期:2016-11-01 00:00:00
abstract::We previously reported that mice deficient in stearoyl-CoA desaturase-1 (Scd1) and maintained on a very low-fat (VLF) diet for 10 days developed severe loss of body weight, hypoglycemia, hypercholesterolemia, and many cholestasis-like phenotypes. To better understand the metabolic changes associated with these phenoty...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00139.2007
更新日期:2008-05-13 00:00:00