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Animal Models of Nephrogenic Diabetes Insipidus
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
Why use Model Organisms for Research?
Model organisms offer a number of benefits over using human subjects for genetics research. One advantage of using model organisms is that specific genes of interest can be knocked out or otherwise modified to observe their effects (1). Additionally, model organisms are often easy to raise within laboratory settings and thus high replicate numbers for studies can be easily generated(2).
Four different mouse lines that model autosomal NDI are cataloged on Mouse Genome Informatics (3). These lines include one line that was heterozygous for mutant and wild type AQP2 (J:113716) and 3 lines homozygous for different AQP2 mutants(J:105809, J:109463, J:121445). Phenotypes associated with mutant Aqp2 within these mice include excessive production of dilute urine and increased thirst, which match the phenotypes seen in human patients.
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Ten total stocks of D. melanogaster found within FlyBase had mutations in Drip proteins(4). Six of these stocks were generated based on inserting transposable elements within the drip gene, 3 by fusion of regulatory sequences with the gene(v51939, v106911, and v51936), and one (66782) by use of a Gal4 gene trap to form a null allele (5). The only phenotypes verified within these strains are that stocks with regulatory fusion constructs lead to lethality or reduced reproductive success of females in some genetic contexts.
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No C. elegans strains specifically meant for modeling NDI or with mutations in aquaporin-6 are labeled within Wormbase(6). However, several stocks are available of worms with a variety of other modified aquaporins, including aquaporin-2, aquaporin-9, aquaporin-4, and aquaporin-8. No phenotypes have been evaluated within these stocks.
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Analysis of Available Model Organisms
Due to the wide variety of already available lines of mice that have modified AQP2, mice are a promising lead as a study organism for NDI. However, the ubiquity of aquaporins across many different organisms gives potential for use of other organisms to do similar functional analysis. Further functional analysis of aquaporins will need to be performed in these organisms to determine the extent of functional conservation between mammals and invertebrates in AQP2 homolog function.
References
1. http://www.biotec.uniba.it/area_docenti/documenti_docente/materiali_didattici/43_knockout.PDF
2. http://www.yourgenome.org/facts/what-are-model-organisms
3.Blake JA, Eppig JT, Kadin JA, Richardson JE, Smith CL, Bult CJ, and the Mouse Genome Database Group. 2017. Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse. Nucl. Acids Res. 2017 Jan. 4;45 (D1): D723-D729. <http://www.informatics.jax.org/>
4.Gramates LS, Marygold SJ, dos Santos G, Urbano J-M, Antonazzo G, Matthews BB, Rey AJ, Tabone CJ, Crosby MA, Emmert DB, Falls K, Goodman JL, Hu Y, Ponting L, Schroeder AJ, Strelets VB, Thurmond J, Zhou P and the FlyBase Consortium. (2017)FlyBase at 25: looking to the future.Nucleic Acids Res. 45(D1):D663-D671 <http://flybase.org/>
5.Stanford, W. L., Cohn, J. B., & Cordes, S. P. (2001). Gene-trap mutagenesis: Past, present and beyond. Nature Reviews Genetics, 2(10), 756-768. doi:10.1038/35093548
6. WormBase 2016: expanding to enable helminth genomic research.Kevin L. Howe, Bruce J. Bolt, Scott Cain, Juancarlos Chan, Wen J. Chen, Paul Davis, James Done, Thomas Down, SibylGao, Christian Grove, Todd W. Harris, Ranjana Kishore, Raymond Lee, Jane Lomax, Yuling Li, Hans-Michael Muller, Cecilia Nakamura, Paulo Nuin, Michael Paulini, Daniela Raciti, Gary Schindelman, Eleanor Stanley, Mary Ann Tuli, Kimberly Van Auken, Daniel Wang, Xiaodong Wang, Gary Williams, Adam Wright, Karen Yook, Matthew Berriman, Paul Kersey, Tim Schedl, Lincoln Stein, Paul W. Sternberg (2016)Nucleic Acids Res, 44, D774-80.<http://www.wormbase.org/#012-34-5>
2. http://www.yourgenome.org/facts/what-are-model-organisms
3.Blake JA, Eppig JT, Kadin JA, Richardson JE, Smith CL, Bult CJ, and the Mouse Genome Database Group. 2017. Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse. Nucl. Acids Res. 2017 Jan. 4;45 (D1): D723-D729. <http://www.informatics.jax.org/>
4.Gramates LS, Marygold SJ, dos Santos G, Urbano J-M, Antonazzo G, Matthews BB, Rey AJ, Tabone CJ, Crosby MA, Emmert DB, Falls K, Goodman JL, Hu Y, Ponting L, Schroeder AJ, Strelets VB, Thurmond J, Zhou P and the FlyBase Consortium. (2017)FlyBase at 25: looking to the future.Nucleic Acids Res. 45(D1):D663-D671 <http://flybase.org/>
5.Stanford, W. L., Cohn, J. B., & Cordes, S. P. (2001). Gene-trap mutagenesis: Past, present and beyond. Nature Reviews Genetics, 2(10), 756-768. doi:10.1038/35093548
6. WormBase 2016: expanding to enable helminth genomic research.Kevin L. Howe, Bruce J. Bolt, Scott Cain, Juancarlos Chan, Wen J. Chen, Paul Davis, James Done, Thomas Down, SibylGao, Christian Grove, Todd W. Harris, Ranjana Kishore, Raymond Lee, Jane Lomax, Yuling Li, Hans-Michael Muller, Cecilia Nakamura, Paulo Nuin, Michael Paulini, Daniela Raciti, Gary Schindelman, Eleanor Stanley, Mary Ann Tuli, Kimberly Van Auken, Daniel Wang, Xiaodong Wang, Gary Williams, Adam Wright, Karen Yook, Matthew Berriman, Paul Kersey, Tim Schedl, Lincoln Stein, Paul W. Sternberg (2016)Nucleic Acids Res, 44, D774-80.<http://www.wormbase.org/#012-34-5>