The protein encoded by the sirt1 gene is an enzyme, SirT1, that couples the hydrolysis of NAD + to the deacetylation of acetyl-lysine residues in substrate proteins. Mutations of the sirt1 gene that fail to encode protein have been introduced into the mouse germ line, and the animals homozygous for these null mutations have various physiological abnormalities. To determine which of the characteristics of these sirt1 −/− mice are a consequence of the absence of the catalytic activity of the SirT1 protein, we created a mouse strain carrying a point mutation (H355Y) that ablates the catalytic activity but does not affect the amount of the SirT1 protein. Mice carrying point mutations in both sirt1 genes, sirt1 Y/Y , have a phenotype that is overlapping but not identical to that of the sirt1-null animals. The sirt1 Y/Y phenotype is significantly milder than that seen in the sirt1 −/− animals. For example, female sirt1 Y/Y animals are fertile, while sirt1 −/− females are sterile. On the other hand, both sirt1 −/− and sirt1 Y/Y male mice are sterile and hypermetabolic. We report that sirt1 Y/Y mice respond aberrantly to caloric restriction, although the effects are more subtle than seen in sirt1 −/− mice. Thus, the SirT1 protein has functions that can be attributed to the catalytic activity of the protein, as well as other functions that are conferred by the protein itself.—Seifert, E. L., Caron, A. Z., Morin, K., Coulombe, J., Hong He, X., Jardine, K., Dewar-Darch, D., Boekelheide, K., Harper, M.-E., McBurney, M. W. SirT1 catalytic activity is required for male fertility and metabolic homeostasis in mice. sirtuin knock-in metabolism Footnotes This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Received August 17, 2011. Accepted September 30, 2011. © FASEB Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print October 17, 2011 , doi: 10.1096/fj.11-193979 February 2012 The FASEB Journal vol. 26 no. 2 555-566 » Abstract Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.11-193979v1 26/2/555 most recent Classifications Research Communications Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Seifert, E. L. Articles by McBurney, M. W. PubMed PubMed citation Articles by Seifert, E. L. Articles by McBurney, M. W. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 26 (2) Alert me to new issues of The FASEB Journal Submit Manuscripts Online Press Room Information for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Activate Online View Collected Papers Breakthroughs in Bioscience Advertising Copyright Permissions Feedback Subscribe to RSS FASEB Publication Services Go to FASEB Online Copyright © 2012 by the Federation of American Societies for Experimental Biology Print ISSN: 0892-6638 Online ISSN: 1530-6860 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23107677-1"); pageTracker._trackPageview();

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