1. Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus.
- Author
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Youn DY, Lee DH, Lim MH, Yoon JS, Lim JH, Jung SE, Yeum CE, Park CW, Youn HJ, Lee JS, Lee SB, Ikawa M, Okabe M, Tsujimoto Y, and Lee JH
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Apoptosis Regulatory Proteins, Cell Count, Cell Death genetics, Cells, Cultured, Embryo Loss blood, Embryo Loss metabolism, Embryo Loss pathology, Embryo, Mammalian, Female, Gene Targeting, Genes, Lethal physiology, Male, Metabolic Diseases blood, Metabolic Diseases genetics, Metabolic Diseases pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Organ Size, Spleen embryology, Thymus Gland embryology, Carrier Proteins genetics, Embryo Loss genetics, Metabolic Diseases embryology, Spleen pathology, Thymus Gland pathology
- Abstract
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 beta-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.
- Published
- 2008
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