【摘要】：缺失突變Nnt基因的C57BL/6J(B6J)小鼠廣泛應(yīng)用于葡萄糖耐受不良癥的代謝研究。該基因在葡萄糖代謝和能量代謝中發(fā)揮重要作用。研究表明缺失Nnt基因的B6J小鼠其胰島素分泌減少,線粒體活性氧增加。本研究中,對比分析了缺失Nnt基因的B6J小鼠和含完整Nnt基因的Km小鼠的血糖水平,并研究了Nnt基因?qū)π∈笊L、飼料轉(zhuǎn)化率性狀的影響,得到如下結(jié)果:1.進化分析結(jié)果表明Nnt基因在多個物種間保守;豬、牛、羊、狗、馬飼養(yǎng)家動物的Nnt基因同源性很高;然而,雞Nnt基因與哺乳動物同源性相對較低。2.發(fā)現(xiàn)兩個品系的小鼠在喂食后血糖水平均逐漸下降,并在空腹24h后達(dá)到最低水平。同時發(fā)現(xiàn),喂食后空腹0h、2h、10h、24h B6J小鼠的血糖水平顯著高于Km小鼠。3.構(gòu)建了B6J×Km F2群體(N=342)。在該群體中,饑餓0到12h的Nnt-/-(缺失Nnt基因)純合子小鼠的血糖變化程度要顯著高于Nnt+/+型(含完整Nnt基因)純合子小鼠(P0.05),Nnt+/-型小鼠的血糖水平與其它兩種基因型小鼠無顯著差異。4.B6J和Km小鼠在5周齡時在體重上呈現(xiàn)顯著差異,但是在三周齡時體重差異不顯著。5.利用F2群體對Nnt基因和代謝、生長、飼料轉(zhuǎn)化率(feed conversion ratio,FCR)性狀進行了關(guān)聯(lián)分析,發(fā)現(xiàn)Nnt基因與3周齡體重(P0.01)、5周齡體重(P0.05)和平均代謝體重(P0.01)顯著關(guān)聯(lián);與平均日采食量、平均日增重、FCR性狀無顯著關(guān)聯(lián)。6.在F2群體中高FCR和低FCR小鼠的血糖水平差異不顯著。7.QRT-PCR結(jié)果表明Nnt基因在腸道、心臟、肝臟和骨骼肌組織中高表達(dá)。在高FCR和低FCR的小鼠中Nnt、Glut-4和Igf-1基因的表達(dá)水平在肝臟組織中差異不顯著。8.F2群體中高FCR小鼠的Glut-1和Ucp-2基因在肝臟中的表達(dá)水平顯著高于低FCR小鼠(P0.05)。低FCR小鼠的Akt-1、Glut-2、Irs-1基因在肝臟中的表達(dá)水平顯著高于高FCR小鼠(P0.05)。9.C2C12細(xì)胞中存在Nnt基因的表達(dá),但是在分化過程中該基因的表達(dá)水平差異不顯著。10.雙熒光素酶報告基因檢測結(jié)果發(fā)現(xiàn),Nnt基因受到miR-221、miR-222調(diào)控。以上結(jié)果說明在小鼠中Nnt基因參與調(diào)控血糖穩(wěn)定、基礎(chǔ)能量代謝和生長性狀存在關(guān)聯(lián),但不影響其飼料效率性狀。另外,Nnt基因可能受到miR-221、miR-222轉(zhuǎn)錄后調(diào)控。這些研究結(jié)果為解釋Nnt基因在代謝和生長中的作用提供了新的依據(jù)。
[Abstract]:C57BL/6J (B6J) mice with deletion mutation Nnt gene are widely used in the metabolism of glucose tolerance. The gene plays an important role in glucose metabolism and energy metabolism. The results showed that the insulin secretion of B6J mice without Nnt gene decreased and the activity of reactive oxygen species (Ros) increased. In this study, the blood glucose levels of B6J mice without Nnt gene and Km mice containing complete Nnt gene were compared and analyzed, and the effects of Nnt gene on the growth and feed conversion rate of mice were studied. the results were as follows: 1. The results of evolutionary analysis showed that the Nnt gene was conserved among many species; the homology of Nnt gene in pigs, cattle, sheep, dogs and horse breeders was very high; however, the homology between chicken Nnt gene and mammals was relatively low. It was found that the blood glucose level of the two strains of mice decreased gradually after feeding, and reached the lowest level after 24 hours on an empty stomach. At the same time, it was found that the blood glucose level of 24 h B6J mice was significantly higher than that of Km mice at 0 h, 2 h and 10 h after feeding. The B6J 脳 Km F2 population (N 鈮，

本文編號：2491712