Smad4基因敲除对小鼠听力和前庭功能的影响

Effect of Smad4 Knockout on Hearing and Vestibular Function of Mouse

卢云云;杨仕明;郭维维;胡吟燕;杨伟炎;杨晓

1:解放军总医院耳鼻咽喉-头颈外科

2:解放军耳鼻咽喉科研究所

3:解放军总医院耳鼻咽喉-头颈外科

4:解放军耳鼻咽喉科研究所

摘要
目的研究Smad4基因敲除(Smad4+/-)小鼠听力和前庭功能的改变。方法检测Smad4基因敲除小鼠(1、2、3、6月龄)与同种同月龄的野生型(Smad4+/+)小鼠的ABR阈值。按Steal的方法测定小鼠的平衡功能,包括游泳试验、空间姿势反射,以及一般行为观察。结果2、3、6月龄Smad4+/-小鼠听力较同种野生型小鼠明显下降,两种基因型小鼠听阈有显著性差异(P<0.01),但1月龄的不同基因型小鼠听力水平无统计学差异(P>0.05)。Smad4基因敲除小鼠与野生型小鼠外观和体重无明显差异(P>0.05),生后至6月龄的Smad4+/-小鼠与野生型小鼠均无前庭功能异常和行为异常。结论单倍体Smad4基因敲除小鼠听力明显障碍,但前庭功能基本正常。表明Smad4对内耳的听觉有重要作用,可能存在着单倍体功能不全性;而单倍体Smad4基因缺失对于前庭功能影响可能不明显。
关键词
Smad4;基因敲除;内耳;听功能;前庭功能
基金项目(Foundation):
国家自然科学基金(30000189);; 军队十五科研基金(01Q050);; 北京市自然科学基金(7042061)资助
作者
卢云云;杨仕明;郭维维;胡吟燕;杨伟炎;杨晓
参考文献

1杨晓,黄培堂,黄翠芬.Smads基因功能的研究进展[J].中国生物化学与分子生物学报,2000,16:145.

2Weinstein M,Yang X,Deng X.Functions of mammalian Smad genes as revealed by targeted gene disruption in mice[J].Cytokine Growth Factor Review,2000,11:49.

3Yang X,Li X,Deng C,et al.The tumor suppressor Smad4/Dpc4is essential for epiblast proliferation and mesoderminductionin mice[J].Proc Natl Acad Sci USA,1998,12:107.

4Xu L,Brodie SG,Yang X,et al.Haploidloss of thetumor suppressor Smad4/Dpc4initiates gastric polyposis and cancer in mice[J].Onco-gene,2000,19:1868.

5Mansour SL.Disruptionof the proto-oncogenint-2in mouse embryo-derived stemcells:ageneral strategyfortargeting mutationsto non-selectable gene[J].Nature,1988,336:348.

6Sanford LP,Ormsby I,Gittenberger-de Groot AC,et al.TGFbeta2knockout mice have multiple developmental defectsthat are non-over-lapping with other TGFbeta knockout phenotypes[J].Development,1997,124:2659.

7Elizabeth MK,Linda E,Thecla B,et al.Effects of a hair cell tran-scriptionfactor,Brn-3.1,gene deletionon homozygous and heterozy-gous mouse cochleas in adulthood and aging[J].Hearing Res,1999,134:71.

8施新猷.医用试验动物学[M].西安.陕西科学技术出版社,1989.

9Thorsten H,Thomas B,Silke RB,et al.Nkx5-1controls semicircu-lar canal formation in the mouse inner ear[J].Development,1998,125:33.

10Deborah P,Lu L,Daniel L,et al.Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4causes developmental defects inthe in-ner ear[J].J Neuroscience,1999,19:5980.

11Thorsten H,Thomas B,Silke RB,et al.Nkx5-1controls semicircu-lar canal formation in the mouse inner ear[J].Development,1998,125:33.

12Hahn SA,Hoque AT,Moskaluk CA,et al.Homozygous deletion map at18q21,1in pancreatic cancer[J].Cancer Res,1996,56:490.

13Pujol R,Hilding D.Anatomy and physiology of the onset of auditory function[J].Acta otolaryngol(Stockh),1973,76:1.

14Morishita H,Makishima T,Kaneko C,et al.Deafness dueto degen-eration of cochlear neurons in caspase-3-deficient mice[J].Bio-chemBio Res Com,2001,284:142.

15Wang W,Edwin K,Shira B,et al.Hmx2homeobox gene control of murine vestibular morphogenesis[J].Development,2001,128:5017.

16Kozel PJ,Friedman RA,Erway LC,et al.Balance and hearing defi-cits in mice with a null mutation in the gene encoding plasma mem-brane Ca2+-ATPase isoform2[J].J Biol Chem,1998,273:18693.