A Study On The Phenotype Of DDB1 Adipose Tissue Specific Konck-out Mice

Currently,with the improvement of life conditions,obesity has become one of the major threats to human health.The imbalance between energy intake and expenditure leads to the accumulation of fat,which is one of the main causes of obesity.Meanwhile,obesity is also a major cause of diabetes,coronary heart disease and other related diseases.DDB1 is an envolutionarily conserved gene that was first isolated as a subunit of a heterodimeric complex that recognises the UV-damaged DNA.The primary research of DDB1 focuses on its role in the nucleotide excision repair pathway.DDB1 and DDB2 form a complex UV-DDB that recognises the UV-damaged DNA and promotes the global genome repair.Moreover,DDB1 and CSA also form a complex which is involved in the transcription-coupled repair.After knocking out DDB1 in S.pombe,C.elegans,Drosophila and mouse,scientists noticed that DDB1 was involved in many other important pathways beyond DNA repair,including that it takes a part in the Cul4-DDB1-ROC1 E3 ligases(CRLs),and function as Cul4-DDB1-DCAF(DDB1-Cul4 associated factors)complex for proteins ubiquitination.Besides,WDTC1 is one of the DCAF proteins.And it is reported that WDTC1 transgenic mice are leaner than wild type mice,for which the adipocyte differentiation of mutations is affected.In order to further clarify how WDTC1 functions as a part of the above complex,we focus on the role of DDB1 in this complex,and explore the effect of DDB1 on adipocyte differentiation.In this thesis,we generated DDB1 adipose tissue specific knock-out mice,namely DDB1-FABP4-Cre mice.We found that the theoretical survival rate of the mutation mice should be 50%,whereas the real survival rate is much lower(male 35%,female 25%).Moreover,compared with the wild type mice,the weight,temperature and blood glucose level of mutation mice is also smaller.Meanwhile,after we isolated the adipose tissue,we found that the volume and weight of adipose tissue was also smaller than the wide type.And the morphology of adipose tissue was changed.Therefore,in the DDB1 adipose tissue specific knock-out mice,the normal life of mice,the morphology and the function of adipocyte tissue was affected,which also lays the foundation of the future research on the function of DDB1.