動(dòng)物模型在生物醫(yī)學(xué)研究中的應(yīng)用

1、動(dòng)物模型在生物醫(yī)學(xué)研究中的應(yīng)用為什么要用動(dòng)物模型進(jìn)行生物醫(yī)學(xué)研究？1、體外實(shí)驗(yàn)不能完全模擬體內(nèi)的環(huán)境2、由于倫理的原因，不能用人體進(jìn)行實(shí)驗(yàn)日軍731人體實(shí)驗(yàn)研究防治疾病與飲水凈化和使用活體人類進(jìn)行生物武器與化學(xué)武器的效果實(shí)驗(yàn) 1946至1948年間，在危地馬拉的監(jiān)獄里展開的一項(xiàng)秘密人體實(shí)驗(yàn) 3、人和動(dòng)物的相似性 有非常相似的器官：心臟、肺、腦等 相似系統(tǒng)系統(tǒng)：呼吸系統(tǒng)、心血管系統(tǒng)、神經(jīng)系統(tǒng)等 以同樣方式執(zhí)行同樣的功能 90%用于治療動(dòng)物的獸醫(yī)手段和治療患者的方法是相似的 5、復(fù)雜性疾病的研究必須借助于動(dòng)物模型復(fù)雜疾病涉及多器官參與及系統(tǒng)調(diào)控代謝，心血管，腫瘤，免疫，神經(jīng)性疾病 復(fù)雜疾病涉及多基

2、因影響和表觀遺傳調(diào)控環(huán)境因素和遺傳因素相互作用 小型動(dòng)物模型是復(fù)雜疾病研究的關(guān)鍵 遺傳背景明確，遺傳操作性強(qiáng)動(dòng)物模型是機(jī)理研究和新藥開發(fā)核心動(dòng)物模型是機(jī)理研究和新藥開發(fā)核心Addiction (monkeys) Alzheimers Disease (mice) Blindness (dogs) Blood Thinners (rats, rabbits, monkeys) Cystic Fibrosis (pigs) Diabetes Type I (mice) Duchenne muscular dystrophy Part 2 (mice) Heart Damage (rats) Hig

3、h Cholesterol (mice, rats, rabbits, dogs, monkeys) HIV/AIDS Part 2 (monkeys, mice) Huntingtons Disease (monkeys) Human Papillomavirus (HPV) vaccine / Cervical Cancer (rabbits, cows, dogs) Influenza also see Swine Flu/Tamiflu (mice) Lebers Congenital Amaurosis (dog) Meningitis B (mice) Multiple Scler

4、osis (mice) Non-Hodgkins Lymphoma and the treatment Rituximab (mice, rats) Paralysis (monkeys) Radiotherapy/Radiation Sickness (mice) SARS (mice) Spinal Cord Injury (rats) TB Vaccine (mice) Trachea Transplant (pigs, cows, dogs, rats, sheep) Tumor Metastasis and more (mice) X-ALD (mice) Mice and rats

5、 account for 95% of animals used in research小鼠是建立疾病模型的最重要實(shí)驗(yàn)動(dòng)物小鼠是建立疾病模型的最重要實(shí)驗(yàn)動(dòng)物生理生化、器官結(jié)構(gòu)及發(fā)育過程和人類相似飼養(yǎng)成本低、易于操作、性成熟早最易于遺傳操作（genetic manipulations）小鼠與人的基因組序列同源性95%，編碼序列99%同源；是唯一的提供了基因組遺傳多樣性，自然變異自然變異表現(xiàn)出比目前的人口存在更多的變異，自然變異可用于識(shí)別各種和數(shù)量性狀及疾病有關(guān)的基因CappechiEvansSmithies20072007年諾貝爾年諾貝爾生理醫(yī)學(xué)獎(jiǎng)生理醫(yī)學(xué)獎(jiǎng)小鼠疾病模型的制作方法相關(guān)的研究計(jì)劃R

6、eciprocal mating between parental inbred strain 129S (red arrow/allele), B6 (black), and C3 (blue) is illustrated, wherein both male and female from one inbred strain are mated to another inbred strain Collaborative Cross (CC) F1 offspring: 129SB6F1, 129SB8F1, 129SC3F1, 129SCF1, 129SNZBF1, 129SPWF1,

7、 129SSJLF1, B6129SF1, B6B8F1, B6C3F1, B6CF1, B6NZBF1, B6PWF1, B6SJLF1, C3129SF1, C3B6F1, C3B8F1, C3CF1, C3NZBF1, C3PWF1, C3SJLF1, B8129SF1, B8B6F1, B8C3F1, B8CF1, B8NZBF1, B8PWF1, B8SJLF1, C129SF1, CB6F1, CB8F1, CC3F1, CNZBF1, CSJLF1, NZB129SF1, NZBB6F1, NZBB8F1, NZBC3F1, NZBCF1, NZBPWF1, NZBSJLF1,

8、PW129SF1, PWB6F1, PWB8F1, PWC3F1, PWCF1, PWNZBF1, PWSJLF1, SJL129SF1, SJLB6F1, SJLB8F1, SJLC3F1, SJLCF1, SJLNZBF1, SJLPWF1.Knockout Mouse Project ConsortiumNature Genetics 36, 921 (2004) North American Conditional Mouse Mutagenesis projectThe Texas A&M Institute for Genomic MedicineEuropean Conditio

9、nal Mouse Mutagenesis ProgramThe Knockout Mouse Project 國(guó)際敲除小鼠聯(lián)盟國(guó)際敲除小鼠聯(lián)盟測(cè)序測(cè)序( (2002)IKMC(2006-12)IMPC(2011-21)聯(lián)合實(shí)驗(yàn)室聯(lián)合實(shí)驗(yàn)室(?-2050?)(?-2050?)KO/transgenic/ENU,radiation/gene trapImmunity &HematopoiesisCardiovascularMetabolismMusculoskeletal& NeurologicalDisease ModelsMechanism studies & Drug screening小鼠疾病模型資源與技術(shù)中心建設(shè)小鼠疾病模型資源與技術(shù)中心建設(shè) 美國(guó)：（MMRRC）UC Davis/UNC/UM/JAX/NCI（5個(gè)中心） 日本: RIKEN BioRC和熊本大學(xué)CARD 英國(guó):Sanger Ce