Abstract:
:We previously constructed a congenic mouse, B6.S-D2Mit194-D2Mit311 (B6.S-2) with 27 Mb of SPRET/Ei donor DNA on distal chromosome 2 in a C57BL/6J background that captured an obesity quantitative trait locus (QTL). Mice homozygous for SPRET/Ei alleles at the donor region had decreased body weight and obesity-related phenotypes (Diament AL, Farahani P, Chiu S, Fisler J, Warden CH. Mamm Genome 15: 452-459, 2004). In this study, we constructed five overlapping subcongenics with smaller SPRET/Ei donor regions to fine map the underlying gene(s). One of the five subcongenic lines derived from the B6.S-2 founding congenic, B6.S-2A, captured the body weight and adiposity phenotypes in a donor region with a maximum size of 7.4 Mb. Homozygous SPRET/Ei donor alleles in both the founding congenic and the derived B6.S-2A subcongenic exhibited significant decreases in body weight, multiple fat pad weights, and adiposity index (total fat pad weight divided by body weight). Interval-specific microarray analysis in four tissues for donor region genes from the founding B6.S-2 congenic identified several differentially expressed genes mapping to the B6.S-2A subcongenic donor region, including prohormone convertase 2 (PC2; gene name: Pcsk2). Quantitative real-time PCR confirmed a modest decrease of PC2 expression in brains of mice homozygous for SPRET/Ei donor alleles. Analysis of the relative levels of mRNA for B6 and SPRET/Ei in heterozygous congenic mice showed differentially higher expression of the C57BL/6J allele over the SPRET/Ei allele, indicating a cis regulation of differential expression. Using subcongenic mapping, we successfully narrowed a body weight and obesity QTL interval and identified PC2 as a positional candidate gene.
journal_name
Physiol Genomicsjournal_title
Physiological genomicsauthors
Chiu S,Kim K,Haus KA,Espinal GM,Millon LV,Warden CHdoi
10.1152/physiolgenomics.00267.2006subject
Has Abstractpub_date
2007-09-19 00:00:00pages
75-85issue
1eissn
1094-8341issn
1531-2267pii
00267.2006journal_volume
31pub_type
杂志文章abstract::Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00115.2010
更新日期:2011-02-11 00:00:00
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::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::Despite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to postmenopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (Ovx) in a...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00228.2010
更新日期:2011-09-22 00:00:00
abstract::Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17beta-estradiol (E2). Specific inhibition of aromatase activity by fadrozo...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00051.2009
更新日期:2009-08-07 00:00:00
abstract::Mouse lines divergently selected for heat loss were evaluated for correlated responses in the hypothalamic transcriptome. High (MH) heat loss mice have approximately 50% greater heat loss, approximately 35% less body fat, approximately 20% greater feed intake, approximately 100% greater locomotor activity levels, and ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00184.2002
更新日期:2003-04-16 00:00:00
abstract::The cardiovascular restricted transcription factor CHF1/Hey2 has been previously shown to regulate the smooth muscle response to growth factors. To determine how CHF1/Hey2 affects the smooth muscle response to growth factors, we performed a genomic screen for transcripts that are differentially expressed in wild-type ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00277.2006
更新日期:2007-06-19 00:00:00
abstract::Psoriasis is a chronic and common human skin disorder currently with no cure. Psoriatic skin displays inflammatory, raised, and scaly lesions with widely aberrant gene expression. Recent studies have revealed critical roles that microRNAs play as a class of posttranscriptional gene regulator in skin development and sk...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00157.2013
更新日期:2014-02-15 00:00:00
abstract::Membrane-bound and membrane-associated proteins are difficult to analyze by mass spectrometry, since the association with lipids impedes the isolation and solubilization of the proteins in buffers suitable for mass spectrometry and the efficient generation of positively charged peptide ions by electrospray ionization....
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00279.2006
更新日期:2007-06-19 00:00:00
abstract::microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through posttranscriptional repression of target genes. miRNAs exert a fundamental level of control over many developmental processes, but their role in the differentiation and development of skeletal muscle from myogenic progenitor cells in hum...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00037.2014
更新日期:2015-03-01 00:00:00
abstract::The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertens...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00074.2012
更新日期:2013-01-07 00:00:00
abstract::The renin-angiotensin system (RAS), known for its roles in cardiovascular, metabolic, and developmental regulation, is present in both the circulation and in many individual tissues throughout the body. Substantial evidence supports the existence of a brain RAS, though quantification and localization of brain renin ha...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00208.2010
更新日期:2011-03-29 00:00:00
abstract::Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of the osterix promoter. To test the role of NFE2L1 in regulating bone formation in v...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00105.2009
更新日期:2010-01-08 00:00:00
abstract::The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. miR-29s are encoded by two gene clusters. Binding sites for several transcriptional factors have been identified in the promoter regions of miR-29 genes. The miR-29 family members share a common seed region sequence and are p...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00141.2011
更新日期:2012-02-27 00:00:00
abstract::Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00124.2016
更新日期:2017-04-01 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::Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00210.2004
更新日期:2005-07-14 00:00:00
abstract::Epigenetic differences between male and female bovine blastocysts provide a plausible link between physiological and gene transcription differences observed between male and female embryos. The aim of this study was to examine sex-related epigenetic differences in bovine blastocysts produced in vitro. Oocytes were mat...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00234.2007
更新日期:2008-01-17 00:00:00
abstract::Adenosine deaminase acting on RNA (ADAR) in Drosophila and mammals has recently become the target of numerous investigations. It is now clear that this protein has a number of functions in the nervous system. Indeed, the mutation of ADAR in Drosophila (dADAR) results in many pathological and physiological changes, suc...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00093.2003
更新日期:2005-01-20 00:00:00
abstract::Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor anal...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00027.2015
更新日期:2015-09-01 00:00:00
abstract::Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00015.2014
更新日期:2014-07-01 00:00:00
abstract::In this paper, two novel, powerful, and robust convolutional neural network (CNN) architectures are designed and proposed for two different classification tasks using publicly available data sets. The first architecture is able to decide whether a given chest X-ray image of a patient contains COVID-19 or not with 98.9...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00084.2020
更新日期:2020-12-01 00:00:00
abstract::We investigated the expression and function of serum response factor (SRF) in endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells (GEnCs) of diabetic nephropathy (DN). The expression of SRF, endothelial markers (VE-cadherin, CD31), and mesenchymal markers (α-SMA, FSP-1, fibronectin) was examined...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00082.2016
更新日期:2016-10-01 00:00:00
abstract::Although increased vascular stiffness is more prominent in aging males than females, and males are more prone to vascular disease with aging, no study has investigated the genes potentially responsible for sex differences in vascular aging. We tested the hypothesis that the transcriptional adaptation to aging differs ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00229.2006
更新日期:2007-04-24 00:00:00
abstract::Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that regulates the oxygen-dependent expression of a number of genes. This transcription factor may contribute to the abundant expression of many genes in renal medullary cells that function normally under hypoxic conditions. The present study was d...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.2001.6.3.159
更新日期:2001-08-28 00:00:00
abstract::Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n = 185) were allotted to a 2 x 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00244.2004
更新日期:2005-05-11 00:00:00
abstract::The purpose of this study was to identify novel transcriptional events occurring in the aortic wall before angiogenesis. We used a defined tissue culture system that takes advantage of the capacity of rat aortic rings to generate neovessels ex vivo in response to angiogenic factor stimulation. Total RNA isolated from ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00048.2006
更新日期:2006-10-03 00:00:00
abstract::Since the discovery of the microbiome in humans, it has been studied in many mammalian species. Different microbiological communities with variable richness and diversity have been found among these species in distinct areas of the reproductive tract. Human studies have shown that the composition of the microbiome is ...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00045.2019
更新日期:2019-08-01 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::Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce fibrosis in rodents after myocardial infarction, resulting in an overall improvement in left ventricular function. Little is known about the effectiveness of BMMNC therapy in hypertensive heart disease. In the current study, we show that deli...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00170.2011
更新日期:2012-10-02 00:00:00