The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention
Open accessAbstract
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.
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Cites
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Cited by
A conditional knockout resource for the genome-wide study of mouse gene function
Skarnes, W. C., Rosen, B., West, A. P., Koutsourakis, M., Bushell, W., Iyer, V., Mujica, A. O., Thomas, M., Harrow, J., Cox, T., et al. (2011) · Nature · doi:10.1038/nature10163 · Cited by 1,708
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Salt Sensitivity of Blood Pressure: A Scientific Statement From the American Heart Association
Elijovich, F., Weinberger, M. H., Anderson, C. A. M., Appel, L. J., Bursztyn, M., Cook, N. R., Dart, R. A., Newton-Cheh, C. H., Sacks, F. M., & Laffer, C. L. (2016) · Hypertension · doi:10.1161/hyp.0000000000000047 · Cited by 482
Metadata
- Authors
- Zambrowicz, B. P., Abuin, A., Ramirez-Solis, R., Richter, L. J., Piggott, J., BeltrandelRio, H., Buxton, E. C., Edwards, J., Finch, R. A., Friddle, C. J., Gupta, A., Hansen, G., Hu, Y., Huang, W., Jaing, C., Key, B. W., Kipp, P., Kohlhauff, B., Ma, Z.-Q., Markesich, D., Payne, R., Potter, D. G., Qian, N., Shaw, J., Schrick, J., Shi, Z.-Z., Sparks, M. J., Van Sligtenhorst, I., Vogel, P., Walke, W., Xu, N., Zhu, Q., Person, C., & Sands, A. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-11-10
- Volume
- 100
- Issue
- 24
- Pages
- 14109-14114
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2131510524
- Cited by
- 332
- References
- 31
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Zambrowicz, B. P., Abuin, A., Ramirez-Solis, R., Richter, L. J., Piggott, J., BeltrandelRio, H., Buxton, E. C., Edwards, J., Finch, R. A., Friddle, C. J., Gupta, A., Hansen, G., Hu, Y., Huang, W., Jaing, C., Key, B. W., Kipp, P., Kohlhauff, B., Ma, Z.-Q., . . . Sands, A. T. (2003). Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2336103100
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
