Cloning, Expression, Purification And Bioassay Of Ciliary Neurotrophic Factor Mutant

Ciliary neurotrophic factor(CNTF) is an 22-26kD acid protein.CNTF was originally purified from chick eye and characterized as a survivability factor for neurons from chick embryonic ciliary ganglia in vitro. It differs from neurophicfactor (NTF ) and has no homologous with NTF.CNTF is not a target-sourcing trophic factor. CNTF is a member of IL-6 family,because of its four helical bundle structure that is similar with LIF and IL-6.CNTF has multiple functions , it is a survival factor for various types of neuron cell and seems to prevent the degeneration of motor axons in vivo and in vitro.CNTF has also been identified as a myotrophic factor for denervated skeletal muscles, enhances nervous system' s development,differentiation and demage recovery. Recent research shows that CNTF,contacting with receptor located in thalamencephalon ,decrease fat and lose weight in ob/ob mice. To diet-induced obesity (DIO) mice model,CNTF has the same function.Noticeably,this model represents the real instance of human obesity.Compared to banting,CNTF has not weight rebound after stopping administration,therefore,it is promisingly developed to a new-type and high-efficient anti-obesity product and has a prevalent clinic development future.CNTF receptor is present in neurons and skeletal muscles widely and is expressed substantively in motor nervous system and related parts. CNTF receptor is composed of three subunits: the CNTF receptor alpha (CNTFR α ), gp130 and the leukemia inhibitory factor receptor β (LIFRβ ). CNTF plays its role through the 130 kDa glycoprotein receptor and transduces through the Janus kinase pathway. The sequence of CNTF receptor subunits is similar with the leptin receptor (LEPR), and their mRNAs are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Ob/ob mice treated with CNTF were found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack a functional leptin receptor, and in mice with diet-induced obesity, which is partially resistant to the actions of leptin. Identification of a cytokine-mediated anti-obesity...