This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Sutherland, A. P. R.
Right arrow Articles by Zhang, W. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sutherland, A. P. R.
Right arrow Articles by Zhang, W. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2009, p. 2804-2815, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01667-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Zinc Finger Protein Zbtb20 Is Essential for Postnatal Survival and Glucose Homeostasis{triangledown}

Andrew P. R. Sutherland,1,2,{dagger} Hai Zhang,3,{dagger} Ye Zhang,3 Monia Michaud,1 Zhifang Xie,3 Mary-Elizabeth Patti,4 Michael J. Grusby,1* and Weiping J. Zhang1,3*

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,1 John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia,2 Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China,3 Research Division, Cellular & Molecular Physiology, Joslin Diabetes Center, and Harvard Medical School, Boston, Massachusetts4

Received 27 October 2008/ Returned for modification 23 November 2008/ Accepted 21 February 2009

Zbtb20 is a member of the POK family of proteins, which function primarily as transcriptional repressors via interactions mediated by their conserved C2H2 Krüppel type zinc finger and BTB/POZ domains. To define the function of Zbtb20 in vivo, we generated knockout mice by homologous recombination. Zbtb20 null mice display a stark phenotype characterized by postnatal growth retardation, metabolic dysfunction, and lethality. Zbtb20 knockout mice displayed abnormal glucose homeostasis, hormonal responses, and depletion of energy stores, consistent with an energetic deficit. Additionally, increased serum bilirubin and alanine aminotransferase levels were suggestive of liver dysfunction. To identify potential liver-specific Zbtb20 target genes, we performed transcript profiling studies on liver tissue from Zbtb20 knockout mice and wild-type littermate controls. These studies identified sets of genes involved in growth, metabolism, and detoxification that were differentially regulated in Zbtb20 knockout liver. Transgenic mice expressing Zbtb20 in the liver were generated and crossed onto the Zbtb20 knockout background, which resulted in no significant normalization of growth or glucose metabolism but a significant increase in life span compared to controls. These data indicate that the phenotype of Zbtb20 knockout mice results from liver-dependent and -independent defects, suggesting that Zbtb20 plays nonredundant roles in multiple organ systems.

* Corresponding author. Mailing address for Michael J. Grusby: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-1240. Fax: (617) 432-0084. E-mail: mgrusby{at}hsph.harvard.edu. Mailing address for Weiping J. Zhang: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Phone and fax: 86-21-8187 1020. E-mail: wzhang{at}smmu.edu.cn

{triangledown} Published ahead of print on 9 March 2009.

{dagger} A. P. R. Sutherland and H. Zhang contributed equally.

Molecular and Cellular Biology, May 2009, p. 2804-2815, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01667-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»