Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus.
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.
Department of Biochemistry, Catholic University of Korea, Korea.
Dong-Ye
DY
Youn
Dong-Hyoung
DH
Lee
Mi-Hyun
MH
Lim
Jung-Sook
JS
Yoon
Ji Hee
JH
Lim
Seung Eun
SE
Jung
Chung Eun
CE
Yeum
Cheol Whee
CW
Park
Ho-Joong
HJ
Youn
Jae-Seon
JS
Lee
Seong-Beom
SB
Lee
Masahito
M
Ikawa
Masaru
M
Okabe
Yoshihide
Y
Tsujimoto
Jeong-Hwa
JH
Lee
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002452:Cell Count; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D020964:Embryo Loss / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian; D005260:Female; D018390:Gene Targeting; D005804:Genes, Lethal / Q000502:physiology; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000196:embryology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D013154:Spleen / Q000196:embryology / Q000473:pathology*; D013950:Thymus Gland / Q000196:embryology / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498806:Bag3 protein, mouse; D002352:Carrier Proteins