A 4.1-Mb congenic region of Rf-4 contributes to glomerular permeability.

Journal of the American Society of Nephrology : JASN
Caitlin C O'MearaHoward J Jacob

Abstract

The combined transfer of two renal function quantitative trait loci (QTLs), Rf-1 (rat chromosome 1) and Rf-4 (rat chromosome 14), from the Fawn-hooded hypertensive rat onto the August Copenhagen Irish genetic background significantly increases proteinuria and demonstrates an interaction between these QTLs. Because the original Rf-4 congenic region is 61.9 Mbp, it is necessary to reduce this interval to feasibly search for variants responsible for renal susceptibility in this region. Here, we generated a minimal congenic line (Rf-1a+4_a) to identify a 4.1-Mb region of the Rf-4 QTL that significantly contributes to the severity of proteinuria in the Fawn-hooded hypertensive rat. Rf-1a+4_a animals have an increased glomerular permeability to albumin without significant changes in BP, indicating that at least one genetic element in this refined region directly affects renal function. Sequence analysis revealed no variants predicted to damage protein function, implying that regulatory elements are responsible for the Rf-4 phenotype. Multiple human studies, including recent genome-wide association studies, link the homologous human region with susceptibility to renal disease, suggesting that this congenic line is an important model f...Continue Reading

References

Dec 1, 1992·Journal of the American Society of Nephrology : JASN·V J SavinD J Welling
Oct 1, 1988·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·W McClellanA Issa
Apr 1, 1995·Journal of the American Society of Nephrology : JASN·B J SprayB I Freedman
Sep 30, 1994·Science·E S Lander, N J Schork
May 1, 1993·Journal of the American Society of Nephrology : JASN·J L SimonsB M Brenner
Apr 1, 1993·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·B I FreedmanV M Buckalew
May 15, 1997·Analytical Biochemistry·M A KesslerO S Wolfbeis
Nov 14, 1997·American Journal of Respiratory and Critical Care Medicine·N J Schork
Mar 26, 1998·Journal of the American Society of Nephrology : JASN·W KrizA P Provoost
Oct 29, 2000·Journal of the American Society of Nephrology : JASN·Masahide ShiozawaHoward J Jacob
Nov 27, 2001·Science·M StollH J Jacob
Dec 6, 2002·Nature·Emmanouil T DermitzakisStylianos E Antonarakis
Jun 24, 2003·Journal of the American Society of Nephrology : JASN·Barry I Freedman
May 22, 2004·Journal of the American Society of Nephrology : JASN·Mark A J Devonald, Fiona E Karet
Sep 2, 2004·Journal of the American Society of Nephrology : JASN·Caroline S FoxDaniel Levy
Mar 11, 2005·Journal of the American Society of Nephrology : JASN·Artur Rangel-FilhoHoward J Jacob
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Nov 24, 2005·American Journal of Physiology. Renal Physiology·Bernardo LópezRichard J Roman
May 5, 2007·Science·Anna HelgadottirKari Stefansson
May 5, 2007·Science·Ruth McPhersonJonathan C Cohen
Dec 19, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keigyou YohMasayuki Yamamoto
Apr 18, 2009·Current Opinion in Nephrology and Hypertension·George Jarad, Jeffrey H Miner
May 12, 2009·Nature Genetics·Anna KöttgenCaroline S Fox
Sep 11, 2009·Nature·Axel ViselLen A Pennacchio
Dec 17, 2009·American Journal of Physiology. Renal Physiology·Hyun Ju Kim, Nosratola D Vaziri
Jan 6, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rikke Nielsen, Erik Ilsø Christensen
May 25, 2010·Biochemical and Biophysical Research Communications·Jaakko Patrakka, Karl Tryggvason
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Aug 12, 2010·PLoS Genetics·Tamra E MeyerUNKNOWN Meta Analysis of Glucose and Insulin Related Traits Consortium
Dec 4, 2010·Journal of the American Society of Nephrology : JASN·Caitlin C O'MearaHoward J Jacob

❮ Previous
Next ❯

Citations

Jun 1, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Angela Schulz, Reinhold Kreutz
Jun 20, 2013·Physiological Genomics·Jozef LazarHoward J Jacob
Feb 8, 2020·Journal of the American Society of Nephrology : JASN·Fan FanRichard J Roman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.