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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 295/6/E1349    most recent 90704.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Youn, D.-Y. Articles by Lee, J.-H. Search for Related Content PubMed PubMed Citation Articles by Youn, D.-Y. Articles by Lee, J.-H.

Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus

¹Department of Biochemistry, ²Department of Internal Medicine, and ³Department of Pathology, College of Medicine, Catholic University of Korea and ⁴Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Science, Seoul, Korea; and ⁵Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, ⁶Department of Medical Genetics, Laboratory of Molecular Genetics, Osaka University Medical School, and ⁷Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, Osaka, Japan

Submitted 18 August 2008 ; accepted in final form 25 September 2008

Bcl-2 interacting cell death suppressor (Bis), also known as Bag3 or CAIR-1, is involved in antistress and antiapoptotic pathways. In addition to Bcl-2, Bis binds to several proteins, suggesting it has diverse functions in normal and pathological conditions. To better define the physiological function of Bis in vivo, we developed bis-deficient mice with a cre-loxP system. Targeted disruption of exon 4 of the bis gene was demonstrated by Southern blotting and PCR, and Western blotting showed that no intact or truncated Bis protein was synthesized in bis^–/– mice. While heterozygotes were fertile and appeared normal, Bis-deficient mice showed growth retardation and died by 3 wk after birth. The relative weight of the thymus and spleen was reduced and the total numbers of white blood cells, splenocytes, and thymocytes were significantly reduced compared with wild-type littermates. Serum profiles indicated significant hypoglycemia as well as decrease in triglyceride and cholesterol levels. Expression profiles of metabolic genes indicated that gluconeogenesis and β-oxidation are activated in the liver of bis^–/– mice. This activation, as well as a decrease in peripheral fat and an induction of fatty liver, appears to be an adaptive response to hypoglycemia. Our study reveals that the absence of Bis has considerable influences on postnatal growth and survival, possibly due to a nutritional impairment.

bis; knockout; hypoglycemia