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The Investigation Of Nicotinamide Nucleotide Transhydrogenase Gene In Glucose And Energy Metabolism

Posted on:2018-10-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:D F A T H I A SuFull Text:PDF
GTID:1313330515495501Subject:Animal breeding and genetics and breeding
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The C57BL/6J(B6J)mice are the most widely utilized strain in a metabolic research of glucose intolerance,which contain a deletion mutation in Nnt gene(exons 7-11).Nnt gene plays important role in glucose and energy metabolism.It has been reported that the mutant Nnt gene resulted in reduced insulin secretion and increased the mitochondrial reactive oxygen species(ROS)in B6 J mice.In this study,the blood glucose level has been comparatively analysed in B6 J and Kunming(Km)mice,which contain the intact Nnt gene.Also,the genetic association has been studied between the Nnt gene and the traits of growth and feed efficiency.The results showed as follows;1.Nnt evolution analysis showed that Nnt m RNA of Mus musculus was closed to Rattus norvegicus in coding regions(cds).Nnt m RNA evolution in Danio rerio was closed to Callorhinchus milii.Whereas,Nnt m RNA of Gallus gallus was not much closed to Xenopus tropicalis and the same Canis lupus familiaris to Sus scrofa.However,Nnt m RNA is closely evolution to each 15 species.2.The blood glucose levels were declined regularly after feeding and reached to the lowest level at 24 hr of fasting in both strains.Moreover,the blood glucose level was significantly higher in B6 J mice than that in Km mice at 0hr(Just after feeding),2hr and 10 hr of fasting.While,the blood glucose level was significantly higher in Km mice than that in B6 J mice at 24 hr of fasting.3.A B6J×Km F2-population(N= 342)was constructed in this study.The variation of glucose level between 0 and 12 hr of fasting of Nnt-/-genotype(Nnt mutant homozygous)mice was significantly higher than that of Nnt +/+ genotype(Nnt intact homozygous)mice in the F2 population(P<0.05).While,the Nnt +/-genotype has no difference with Nnt-/-or Nnt +/+ genotype mice.4.There were significant differences between body weights of B6 J and Km mice at 5weeks of age.While,no significant differences were observed between B6 J and Km body weights at 3 weeks of age.5.The correlation between Nnt gene and metabolism,growth and feed conversion efficiency ratio(FCR)traits of mice were performed using the F2 population.The results showed that Nnt gene was significantly associated with the body weight of 3weeks(IBW)(P<0.01)and 5 weeks(FBW)(P<0.05)as well as average metabolic body weight(AMBW)(P<0.01),but not associated with average daily feed intake(AFI),average daily gain(ADG)and FCR traits.6.The blood glucose level was not much different between the high-FCR and lowFCR mice.7.The Nnt gene was highly expressed at intestine,heart,lung and skeletal muscle tissues.The expression levels of Nnt,Glut-4 and Igf-1 genes in liver tissues were not significantly different between high-FCR and low-FCR mice.8.The expression levels of Glut-1 and Ucp-2 genes were significantly higher in the high-FCR mice than that in the low-FCR mice.While,the expression levels of Akt-1,Glut-2 and Irs-1 genes were significantly higher in the low-FCR mice than that in the high-FCR mice(P<0.05).9.Nnt gene was expressed in C2C12 cells,and the expression level was not much different during differentiation.10.The dual-luciferase reporter assay indicated that the Nnt gene could be targeted by mi R-221 and mi R-222 in C2C12 myoblast cells.These results indicate that Nnt gene is related to glucose stability,basal energy metabolism and growth,but not to feed efficiency traits in mice.This study offered novel evidences to the role of Nnt gene on metabolism and growth.Further,the Nnt gene could be regulated by mi R-221 and mi R-222.
Keywords/Search Tags:Nnt, blood glucose level, average daily feed intake, feed conversion ratio, mice
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