Deletion of Irs2 Causes Reduced Kidney Size in Mice: Role for Inhibition of GSK3β?

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Deletion of Irs2 Causes Reduced Kidney Size in Mice: Role for Inhibition of GSK3β?

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dc.contributor.author Carew, Rosemarie M
dc.contributor.author Goldschmeding, Roel
dc.contributor.author Martin, Finian
dc.contributor.author Brazil, Derek P
dc.contributor.author Sadagurski, Marianna
dc.contributor.author White, Morris Francis
dc.date.accessioned 2011-11-29T16:17:27Z
dc.date.issued 2010
dc.identifier.citation Carew, Rosemarie M., Marianna Sadagurski, Roel Goldschmeding, Finian Martin, Morris F. White, and Derek P. Brazil. 2010. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3β? BMC Developmental Biology 10: 73. en_US
dc.identifier.issn 1471-213X en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5355305
dc.description.abstract Background: Male \(Irs2^{-/-}\) mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in \(Irs2^{-/-}\) mice. We identify retarded renal growth in male and female \(Irs2^{-/-}\) mice, independent of diabetes. Results: Kidney size and kidney:body weight ratio were reduced by approximately 20% in \(Irs2^{-/-}\) mice at postnatal day 5 and was maintained in maturity. Reduced glomerular number but similar glomerular density was detected in \(Irs2^{-/-}\) kidney compared to wild-type, suggesting intact global kidney structure. Analysis of insulin signalling revealed renal-specific upregulation of PKBβ/Akt2, hyperphosphorylation of GSK3β and concomitant accumulation of β-catenin in \(Irs2^{-/-}\) kidney. Despite this, no significant upregulation of β-catenin targets was detected. Kidney-specific increases in Yes-associated protein (YAP), a key driver of organ size were also detected in the absence of Irs2. YAP phosphorylation on its inhibitory site Ser127 was also increased, with no change in the levels of YAP-regulated genes, suggesting that overall YAP activity was not increased in \(Irs2^{-/-}\) kidney. Conclusions: In summary, deletion of Irs2 causes reduced kidney size early in mouse development. Compensatory mechanisms such as increased β-catenin and YAP levels failed to overcome this developmental defect. These data point to Irs2 as an important novel mediator of kidney size. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1471-213X-10-73 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910663/pdf/ en_US
dash.license LAA
dc.title Deletion of Irs2 Causes Reduced Kidney Size in Mice: Role for Inhibition of GSK3β? en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal BMC Developmental Biology en_US
dash.depositing.author Sadagurski, Marianna
dc.date.available 2011-11-29T16:17:27Z
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US

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