CAJ | 학술논문

目的确定人类常染色体隐性遗传性多囊肾病(ARPKD)致病基因Pkhd1在ApcMin/小鼠肠道肿瘤发生中的作用.方法 Pkhd1基因敲除小鼠模型(Pkhd1-/-)与肠道肿瘤模型ApcMin/+小鼠杂交后,比较不同月龄(1、3、6月)单一ApcMin/+小鼠与缺失Pkhd1的ApcMin/+小鼠(Pkhd1-/-;ApcMin)肠道肿瘤的数目及大小,并观察其肠道肿瘤组织病理的变化.结果与单一的ApcMin/+小鼠相比,Pkhd1-/-;ApcMin/+小鼠在1月龄时,肠道肿瘤数目及大小均无显著差异.但该小鼠在3月龄和6月龄时肠道肿瘤数目及大小均显著增加(P=0.017、P=0.022).此外,在6月龄时,Pkhd1-/-;ApcMin/+小鼠病理表型有向恶性转化的明显趋势.结论具有Pkhd1缺失的Apc Min/+小鼠与单一的ApcMin/小鼠相比能够显著促进肠道肿瘤的发生和发展,并具有促进其肿瘤恶性转化的趋势.
목적 학정인류상염색체은성유전성다낭신병(ARPKD)치병기인Pkhd1재ApcMin/소서장도종류발생중적작용.방법 Pkhd1기인고제소서모형(Pkhd1-/-)여장도종류모형ApcMin/+소서잡교후,비교불동월령(1、3、6월)단일ApcMin/+소서여결실Pkhd1적ApcMin/+소서(Pkhd1-/-;ApcMin)장도종류적수목급대소,병관찰기장도종류조직병리적변화.결과 여단일적ApcMin/+소서상비,Pkhd1-/-;ApcMin/+소서재1월령시,장도종류수목급대소균무현저차이.단해소서재3월령화6월령시장도종류수목급대소균현저증가(P=0.017、P=0.022).차외,재6월령시,Pkhd1-/-;ApcMin/+소서병리표형유향악성전화적명현추세.결론 구유Pkhd1결실적Apc Min/+소서여단일적ApcMin/소서상비능구현저촉진장도종류적발생화발전,병구유촉진기종류악성전화적추세.
Objective To investigate the role of Pkhd1,an ARPKD casual gene,in intestinal tumorigenesis of ApcMin/+ mice.Methods ApcMin/+ mice were crossed with Pkhd1 knockout mice (Pkhd1-/-) to produce compound Pkhd1-/-; ApcMin/+ mice.The tumorigenic susceptibility between Pkhd1-/-; ApcMin/+ and ApcMin/+ mice was compared.The number,size and pathology of tumors were analyzed at the age of 1,3,and 6 months.Results There was no statistical difference in tumor number and size between 1 month-old ApcMin/+ and Pkhd1-/-;ApcMin/+ mice.However,the number and size of the intestinal tumors in 3 and 6 month-old Pkhd1-/-; ApcMin/+ mice were significantly larger than that of ApcMin/+ mice respectively (P =0.017,P =0.022).In addition,compared to 6 month-old ApcMin/+ mice,more malignant transformation was also pathologically observed in the age-matched Pkhd1-/-;ApcMin/+ mice.Conclusion Loss of Pkhd1 likely promotes the intestinal tumorigenesis and tumor malignant transformation in ApcMin/+ mice.