NDLI: Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention

Content Provider	PubMed Central
Author	Zambrowicz, Brian P. Abuin, Alejandro Ramiro, Ramirez-solis Richter, Lizabeth J. Piggott, James Hector, Beltrandelrio Buxton, Eric C. Edwards, Joel Finch, Rick A. Friddle, Carl J. Gupta, Anupma Hansen, Gwenn Hu, Yi Huang, Wenhu Crystal, Jaing Key, Billie Wayne Kipp, Peter Buckley, Kohlhauff Ma, Zhi-qing Diane, Markesich Payne, Robert Potter, David G. Qian, Ny Shaw, Joseph Schrick, Jeff Shi, Zheng-zheng Sparks, Mary Jean Van, Sligtenhorst Isaac Vogel, Peter Walke, Wade Xu, Nianhua Zhu, Qichao Person, Christophe Sands, Arthur T.
Copyright Year	2003
Abstract	The availability of both the mouse and human genome sequences allows for the systematic discovery of human gene function through the use of the mouse as a model system. To accelerate the genetic determination of gene function, we have developed a sequence-tagged gene-trap library of >270,000 mouse embryonic stem cell clones representing mutations in ≈60% of mammalian genes. Through the generation and phenotypic analysis of knockout mice from this resource, we are undertaking a functional screen to identify genes regulating physiological parameters such as blood pressure. As part of this screen, mice deficient for the Wnk1 kinase gene were generated and analyzed. Genetic studies in humans have shown that large intronic deletions in WNK1 lead to its overexpression and are responsible for pseudohypoaldosteronism type II, an autosomal dominant disorder characterized by hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Consistent with the human genetic studies, Wnk1 heterozygous mice displayed a significant decrease in blood pressure. Mice homozygous for the Wnk1 mutation died during embryonic development before day 13 of gestation. These results demonstrate that Wnk1 is a regulator of blood pressure critical for development and illustrate the utility of a functional screen driven by a sequence-based mutagenesis approach.
Related Links	http://dx.doi.org/10.1073/pnas.2336103100
Ending Page	14114
Page Count	6
Starting Page	14109
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-11-25
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention

Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor

Two ways to trap a gene in mice

Polymorphisms in the WNK1 Gene Are Associated with Blood Pressure Variation and Urinary Potassium Excretion

Global transcriptional responses to cisplatin in Dictyostelium discoideum identify potential drug targets

An efficient proteomics method to identify the cellular targets of protein kinase inhibitors

WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl−-transporting epithelia

WNK1 kinase isoform switch regulates renal potassium excretion

A Large-Scale Gene-Trap Screen for Insertional Mutations in Developmentally Regulated Genes in Mice

Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention

Similar Documents

Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention

Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor

Two ways to trap a gene in mice

Polymorphisms in the WNK1 Gene Are Associated with Blood Pressure Variation and Urinary Potassium Excretion

Global transcriptional responses to cisplatin in Dictyostelium discoideum identify potential drug targets

An efficient proteomics method to identify the cellular targets of protein kinase inhibitors

WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl−-transporting epithelia

WNK1 kinase isoform switch regulates renal potassium excretion

A Large-Scale Gene-Trap Screen for Insertional Mutations in Developmentally Regulated Genes in Mice

Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention