It may be particularly useful for producing animal models for hypomorphic gene function.
Xia Xugang, Wang Hongyan, Qiu Linghua, Zhou Hongxia, Xu Zuoshang 2008, 'A construct with fluorescent indicators for conditional expression of miRNA', BMC Biotechnologyhttp://www.biomedcentral.com/1472-6750/8/77. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
The consequences of the presence of two hypomorphic variants have been poorly documented in literature.
S Pandita, D Khullar, R Saxena, I C Verma 2018, 'Autosomal dominant polycystic kidney disease: Presence of hypomorphic alleles in PKD1Gene', Indian Journal of Nephrologyhttp://www.indianjnephrol.org/article.asp?issn=0971-4065;year=2018;volume=28;issue=6;spage=482;epage=484;aulast=Pandita. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
These alleles are hypomorphic and show lighter pigmentation phenotypes of the body and eyes.
Anil K Challa, Evan R Boitet, Ashley N Turner, Larry W Johnson, Daniel Kennedy, EthanR Downs, Katherine M Hymel, Alecia K Gross, Robert A Kesterson 2016, 'Novel Hypomorphic Alleles of the Mouse Tyrosinase Gene Induced by CRISPR-Cas9 NucleasesCause Non-Albino Pigmentation Phenotypes.', PLoS ONEhttp://europepmc.org/articles/PMC4880214?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
This functional analysis suggested that the mutant allele has hypomorphic effects.
Tomoko Uehara, Hidenori Suzuki, Nobuhiko Okamoto, Tatsuro Kondoh, Ayesha Ahmad, BridgetC. O'Connor, Sawako Yoshina, Shohei Mitani, Kenjiro Kosaki, Toshiki Takenouchi 2019, 'Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study usingplatelets in patients and functional studies in a Caenorhabditis elegans model', Scientific Reportshttp://link.springer.com/article/10.1038/s41598-019-40988-7. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
This hypomorphic allele causes progressive tissue-specific pathologies, including hearing loss, reduced adiposity, adipose tissue dysfunction, and hypertrophic cardiomyopathy.
Thomas Agnew, Michelle Goldsworthy, Carlos Aguilar, Anna Morgan, Michelle Simon, HelenHilton, Chris Esapa, Yixing Wu, Heather Cater, Liz Bentley, Cheryl Scudamore, JoannaPoulton, Karl J. Morten, Kyle Thompson, Langping He, Steve D.M. Brown, Robert W. Taylor,Michael R. Bowl, Roger D. Cox 2018, 'A Wars2 Mutant Mouse Model Displays OXPHOS Deficiencies and Activation of Tissue-SpecificStress Response Pathways', Cell Reportshttp://www.sciencedirect.com/science/article/pii/S2211124718318710. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Comparison of the phenotypes of the hypomorphic and knock-out alleles provides evidence of two independent roles in photoreceptor development.
Mailin Sotolongo-Lopez, Karen Alvarez-Delfin, Carole J Saade, Daniel L Vera, JamesM Fadool 2016, 'Genetic Dissection of Dual Roles for the Transcription Factor six7 in PhotoreceptorDevelopment and Patterning in Zebrafish.', PLoS Geneticshttp://europepmc.org/articles/PMC4825938?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions.
Erica P Homan, Caressa Lietman, Ingo Grafe, Jennifer Lennington, Roy Morello, DobrawaNapierala, Ming-Ming Jiang, Elda M Munivez, Brian Dawson, Terry K Bertin, Yuqing Chen,Rhonald Lua, Olivier Lichtarge, John Hicks, Mary Ann Weis, David Eyre, Brendan H LLee 2014, 'Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.', PLoS Geneticshttp://europepmc.org/articles/PMC3900401?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
However, it did cause the formation of hypomorphic limbs as a result of increased cellular condensation and apoptosis.
Finnson Kenneth, Berdugo Jérémie, Michaud Pierre-Luc, Lévesque Mathieu, Guimond Jean-Charles,Philip Anie, Roy Stéphane 2010, 'BMP-2 functions independently of SHH signaling and triggers cell condensation andapoptosis in regenerating axolotl limbs', BMC Developmental Biologyhttp://www.biomedcentral.com/1471-213X/10/15. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
This observation can explain the heightened sensitivity of nonexchange chromosomes to the meiotic effects of hypomorphic ald alleles.
William D Gilliland, Stacie E Hughes, Jeffrey L Cotitta, Satomi Takeo, Youbin Xiang,R Scott Hawley 2007, 'The multiple roles of mps1 in Drosophila female meiosis.', PLoS Geneticshttp://europepmc.org/articles/PMC1914070?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)