title: Allele compensation in tip60+/- mice rescues white adipose tissue function in vivo.
abstract: Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice.
authors.affiliation: Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Netherlands Metabolomics Center, Leiden, The Netherlands.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Netherlands Metabolomics Center, Leiden, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hamers
authors.affiliation: Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rakhshandehroo
authors.affiliation: Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Netherlands Metabolomics Center, Leiden, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Berger
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Lough
authors.affiliation: Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Netherlands Metabolomics Center, Leiden, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Kalkhoven
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology; D052436:Adipose Tissue, White / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004303:Dosage Compensation, Genetic / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D017931:DNA Primers; D015534:Trans-Activators; D051548:Histone Acetyltransferases; C523065:Kat5 protein, mouse; D000074443:Lysine Acetyltransferase 5