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化学物质诱发的小鼠肢体畸形动物模型的建立

Development of mouse model of limb malformation induced by chemical

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【作者】 陈蓉芳张天宝印木泉朱江波郭苗莉

【Author】 CHEN Rong Fang,ZHANG Tian Bao *,YIN Mu Quan,ZHU Jiang Bo,GUO Miao Li(Department of Health Toxicology,College of Basic Medical Sciences,Second Military Medical University,Shanghai 200433,China) [

【机构】 第二军医大学基础医学部卫生毒理学教研室第二军医大学基础医学部卫生毒理学教研室 上海200433上海200433上海200433

【摘要】 目的 :建立发生率稳定、畸形类型特异和易于获得的化学物质所致小鼠肢体畸形动物模型。 方法 :采用致突变性致畸物 N-甲基 - N’-硝基 - N-甲基亚硝基胍 (N- m ethyl- N’- nitro- N- nitrosoguanidine,MNNG)作为受试物 ,观察不同剂量和不同给药时间的胎鼠畸形率、畸形类型及特征。结果 :孕期第 12天一次给予 MNNG4 0 m g/ kg时 ,胎鼠畸形类型主要为肢体畸形 ,肢体畸形率以活胎计为 33.7% (31/ 92 ) ,以窝计为 81.8% (9/ 11) ,肢体畸形占畸形胎鼠的构成比为 10 0 %。畸形类型以短指 (趾 )和缺指 (趾 )最常见。四肢畸形的发生率和严重程度存在不对称性 ,依次为左后 >左前 >右后 >右前。掌跖骨缺失和骨化不全发生率较高 ,此外还有胫腓骨的缺失和骨化不全 ,特别是大体形态所见短肢是胫腓骨缺失所致。结论 :成功建立了小鼠肢体畸形动物模型 ,为进一步研究肢体畸形的分子机制奠定了基础

【Abstract】 Objective: To develop a convenient, stable animal model of unique limbs malformation type with chemical teratogens. Methods: N methyl N’ nitro N nitrosoguanidine(MNNG), a mutagenic teratogen,was used to induce ICR mice embryo limb malformation.The spectrum of malformation,the rate and character of limb defects of different dosage and exposure time were observed.Results: Limb defect was the main type on gestational day 12 with 40 mg/kg of MNNG.It was also found that the occurrence and severity were unsymmetric,limbs on the left side were more frequently malformed than limbs on the right side,and hindlimbs were more frequently malformed than forelimbs.The incidence of fetal limb defects was 33.7% in total living fetuses and 81.8% in total litters.Malformation was all limb defects.The phenotypes of affected limb mainly included oligodactyly,truncated limb and polydactyly.Skeletal preparation showed that the loss of tibia and fibia led to the truncated limbs.Conclusion: An animal model of limb malformation for studying the molecular mechanism of chemical teratogens is established successfully.

【基金】 国家自然科学基金 ( 3 9870 65 7)
  • 【文献出处】 第二军医大学学报 ,Academic Journal of Second Military Medical University , 编辑部邮箱 ,2003年06期
  • 【分类号】R-332
  • 【被引频次】5
  • 【下载频次】72
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