遗传 ›› 2021, Vol. 43 ›› Issue (4): 375-384.doi: 10.16288/j.yczz.21-005
• 资源与平台 • 上一篇
收稿日期:
2021-01-05
修回日期:
2021-03-04
出版日期:
2021-04-20
发布日期:
2021-04-20
通讯作者:
刘志玮
E-mail:liuzhiwei@cam-su.org
作者简介:
朱文静,硕士,实验技术员,研究方向:生物化学与分子生物学。E-mail: 基金资助:
Received:
2021-01-05
Revised:
2021-03-04
Online:
2021-04-20
Published:
2021-04-20
Contact:
Liu Zhiwei
E-mail:liuzhiwei@cam-su.org
Supported by:
摘要:
小鼠发育代谢表型库(Mouse Developmental and Metabolic Phenotype Repository, MDMPR)是一个致力于小鼠资源和表型数据实时共享的开放性平台,它依托于科技部重点研发计划“发育编程及其代谢调节”专项项目“建立小鼠发育代谢表型库”。该项目预计在5年内完成500个发育代谢相关小鼠敲除模型的建立,并对其表型数据进行标准化的解析、建立表型数据库。MDMPR作为一个资源及数据集成的库,由多个子系统作为支撑,包括ES细胞数据库、项目管理系统、繁育管理系统、精子库管理系统、表型分析系统,信息化管理深入到项目中每个环节,从基因突变ES细胞制备、基因突变小鼠制备、小鼠繁育,精子冻存到最终的表型分析、数据处理及展示,保证了MDMPR产生数据的真实性及实时性。MDMPR除了不断地推进项目进行,增加自身产生的数据外,也在积极的整合其他的资源及数据,如人特异性基因敲除ES细胞库、蛋白相互作用数据库(STRING)、核心转录调节环路(dbCoRc)和Enhancer-Indel数据库,今后还将进一步整合,帮助发育代谢及其他领域的研究人员能够一站式的获取所需资源和数据、加快研究进程,最终服务于全人类的医疗事业。
朱文静, 刘志玮. MDMPR:小鼠发育代谢表型库[J]. 遗传, 2021, 43(4): 375-384.
Wenjing Zhu, Zhiwei Liu. MDMPR: Mouse Developmental and Metabolic Phenotype Repository[J]. Hereditas(Beijing), 2021, 43(4): 375-384.
图1
基于突变小鼠胚胎干细胞的敲除策略 “Knockout First” allele (tm1a)是在目的基因内含子中插入一个SA-IRES-reporter片段(含有报告基因lacZ和一个启动子驱动的Neo),lacZ的转录在SA的作用下受目的基因启动子控制,并在polyA处终止,从而达到终止目的基因转录、破坏基因表达的目的。Flp的表达可以删除SA-IRES-reporter片段,将tm1a转变成条件敲除基因(tm1c),从而恢复基因功能。在tm1a的基础上,Cre的表达可以删除Neo和critical region从而变成lacZ标记的allele (tm1b)同时敲除基因;在tm1c的基础上,Cre的表达可以删除tm1c allele上的critical region而变成移码突变的tm1d,从而使该基因不表达。"
附表1
CAM-SU GRC微生物质控标准"
病原体 | 检测项目 | 英文名称 | 质控标准 |
---|---|---|---|
病毒 | 鼠痘病毒 | ECT (Mousepox (Ectromelia) Virus) | 国标必检项 |
小鼠肝炎病毒 | MHV (Mouse hepatitis virus) | 国标必检项 | |
仙台病毒 | SV (Sendai virus) | 国标必检项 | |
小鼠肺炎病毒 | PVM (Pneumonia virus of Mice) | 国标必检项 | |
呼肠孤病毒Ⅲ型 | REO-3 (Reovirus type 3) | 国标必检项 | |
小鼠细小病毒(MVM株) | MVM (Minute virus of Mice) | 国标必检项 | |
汉坦病毒 | HV (Hantavirus) | 国标选做项 | |
淋巴细胞脉络丛脑膜炎病毒 | LCMV (Lymphocytic choriomeningitis virus) | 国标选做项 | |
小鼠脑脊髓炎病毒 | TMEV (Theiler’s mouse encephalomyelitis virus) | 国标选做项 | |
小鼠腺病毒 | MAV (Mouse adenovirus type 1(FL) & 2(K87)) | 国标选做项 | |
多瘤病毒 | Poly (Polyoma virus) | 国标选做项 | |
小鼠轮状病毒 | EDIM (Mouse rotavirus) | 国际标准选做项 | |
小鼠巨细胞瘤病毒 | MCMV (Mouse Cytomegalovirus) | 国际标准选做项 | |
乳酸脱氢酶增高病毒 | LDV (Lactate dehydrogenase-elevating virus) | 国际标准选做项 | |
小鼠细小病毒 | MPV (Mouse parvovirus) | 国际标准选做项 | |
小鼠细小病毒NS-1 | PARV-NS1 (Parvovirus NS-1) | 国际标准选做项 | |
K病毒 | K virus | 国际标准选做项 | |
小鼠诺如病毒 | MNV (Murine norovirus) | 国际标准选做项 | |
病原菌 | 支原体 | MYCO (Mycoplasma) | 国标选做项 |
沙门菌 | SALM (Salmonella spp.) | 国标必检项 | |
鼠棒状杆菌 | CKUT (Corynebacterium kutscheri) | 国标必检项 | |
泰泽病原体 | CPIL (Clostridium piliforme (Tyzzer’s organism)) | 国标必检项 | |
噬肺巴斯德杆菌 | PPNE (Pasteurella pneumotropica) | 国标必检项 | |
金黄色葡萄球菌 | SAUR (Staphylococcus aureus) | 国标必检项 | |
绿脓杆菌 | PAER (Pseudomonsa aeruginosa) | 国标必检项 | |
肺炎克雷伯氏杆菌 | KPNE (Klebsiella pneumonia) | 国标必检项 | |
肺炎链球菌 | SPNE (Streptococcus pneumonia) | 国标选做项 | |
乙型溶血性链球菌 | BHS (Streptococcus (Beta-hemolytic)) | 国标选做项 | |
多杀巴斯德杆菌 | PMUL (Pasteurella multocida) | 国标选做项 | |
枸橼酸杆菌 | CROD (Citrobacter rodentium) | 国际标准选做项 | |
支气管鲍特杆菌 | BBRO (Bordetella bronchiseptica) | 国标选做项 | |
产酸克雷伯氏杆菌 | KOXY (Klebsiella oxytoca) | 国际标准选做项 | |
肺炎支原体 | MPUL (Mycoplasma pulmonis) | 国标必检项 | |
奇异变形杆菌 | PMIR (Proteus mirabilis) | 国际标准选做项 | |
乙型溶血性链球菌B群 | GBBHS (Beta strep.Sp.Group B) | 国标选做项 | |
乙型溶血性链球菌G群 | GGBHS (Beta strep.Sp.Group G) | 国标选做项 | |
寄生虫 | 体外寄生虫 | ECTO (Ectoparasites) | 国标必检项 |
弓形虫 | TOXO (Toxoplasma gondii) | 国标必检项 | |
全部蠕虫 | HELM (All Helminths) | 国标必检项 | |
鞭毛虫 | FLAG (Flagellates) | 国标必检项 | |
纤毛虫 | CILI (Ciliates) | 国标选做项 | |
兔脑原虫 | ECUN (Encephalitozoon cuniculi) | 国标选做项 |
附表2
MARC微生物质控标准"
病原体 | 检测项目 | 英文名称 | 检测方法 |
---|---|---|---|
病毒 | 鼠痘病毒 | ECT (Mousepox (Ectromelia) Virus) | 国标必检项 |
小鼠肝炎病毒 | MHV (Mouse hepatitis virus) | 国标必检项 | |
仙台病毒 | SV (Sendai virus) | 国标必检项 | |
小鼠肺炎病毒 | PVM (Pneumonia virus of Mice) | 国标必检项 | |
呼肠孤病毒Ⅲ型 | REO-3 (Reovirus type 3) | 国标必检项 | |
汉坦病毒 | HV (Hantavirus) | 国标选做项 | |
淋巴细胞脉络丛脑膜炎病毒 | LCMV (Lymphocytic choriomeningitis virus) | 国标选做项 | |
小鼠脑脊髓炎病毒 | TMEV (Theiler’s mouse encephalomyelitis virus) | 国标选做项 | |
小鼠腺病毒 | MAV (Mouse adenovirus type 1(FL) & 2(K87)) | 国标选做项 | |
多瘤病毒 | Poly (Polyoma virus) | 国标选做项 | |
小鼠轮状病毒 | EDIM (Mouse rotavirus) | 国际标准选做项 | |
小鼠巨细胞瘤病毒 | MCMV (Mouse Cytomegalovirus) | 国际标准选做项 | |
小鼠细小病毒 | MPV (Mouse parvovirus) | 国际标准选做项 | |
K病毒 | K virus | 国际标准选做项 | |
病原菌 | 肺支原体 | MPUL (Mycoplasma pulmonis) | 国标必检项 |
沙门菌 | SALM (Salmonella spp.) | 国标必检项 | |
鼠棒状杆菌 | CKUT (Corynebacterium kutscheri) | 国标必检项 | |
泰泽病原体 | CPIL (Clostridium piliforme (Tyzzer’s organism)) | 国标必检项 | |
噬肺巴斯德杆菌 | PPNE (Pasteurella pneumotropica) | 国标必检项 | |
金黄色葡萄球菌 | SAUR (Staphylococcus aureus) | 国标必检项 | |
绿脓杆菌 | PAER (Pseudomonsa aeruginosa) | 国标必检项 | |
肺炎克雷伯氏杆菌 | KPNE (Klebsiella pneumonia) | 国标必检项 | |
肺炎链球菌 | SPNE (Streptococcus pneumonia) | 国标选做项 | |
乙型溶血性链球菌 | BHS (Streptococcus (Beta-hemolytic)) | 国标选做项 | |
皮肤病原真菌 | Pathogenic dermal fungi | 国标选做项 | |
假结核耶尔森菌 | Yersinia pseudotuberculosis | 国标选做项 | |
小肠结肠炎耶尔森菌 | Yesinia enterocolitica | 国标选做项 | |
念珠状链杆菌 | Streptobacillus moniliformis | 国标选做项 | |
大肠埃希菌O115 a,C,K(B) | Escherichia coli O115 a,C,K(B) | 国标选做项 | |
纤毛相关呼吸道杆菌 | CARB (Cilia-Associated Respiratory Bacillus) | 国际标准选做项 | |
寄生虫 | 体外寄生虫 | ECTO (Ectoparasites) | 国标必检项 |
弓形虫 | TOXO (Toxoplasma gondii) | 国标必检项 | |
蠕虫 | HELM (Helminth) | 国标必检项 | |
鞭毛虫 | FLAG (Flagellates) | 国标必检项 | |
卡式肺孢子虫 | Pneumocystis carinii | 国标选做项 | |
小鼠脑炎原虫 | ECUN (Encephalitozoon cuniculi) | 国标选做项 |
[1] |
Freudenthal B, Logan J, Pipelines SIM, Croucher PI, Williams GR, Bassett JHD. Rapid phenotyping of knockout mice to identify genetic determinants of bone strength. J Endocrinol, 2016,231(1):R31-46.
doi: 10.1530/JOE-16-0258 pmid: 27535945 |
[2] |
Mishra A, Bubela T. Legal agreements and the governance of research commons: lessons from materials sharing in mouse genomics. OMICS, 2014,18(4):254-273.
doi: 10.1089/omi.2013.0158 |
[3] |
Adams D, Baldock R, Bhattacharya S, Copp AJ, Dickinson M, Greene NDE, Henkelman M, Justice M, Mohun T, Murray SA, Pauws E, Raess M, Rossant J, Weaver T, West D. Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening. Dis Model Mech, 2013,6(3):571-579.
doi: 10.1242/dmm.011833 |
[4] |
Sung YH, Baek IJ, Seong JK, Kim JS, Lee HW. Mouse genetics: catalogue and scissors. BMB Rep, 2012,45(12):686-692.
doi: 10.5483/bmbrep.2012.45.12.242 pmid: 23261053 |
[5] |
Mallon AM, Iyer V, Melvin D, Morgan H, Parkinson H, Brown SDM, Flicek P, Skarnes WC. Accessing data from the International Mouse Phenotyping Consortium: state of the art and future plans. Mamm Genome, 2012,23(9-10):641-652.
doi: 10.1007/s00335-012-9428-9 |
[6] |
Auwerx J, Avner P, Baldock R, Ballabio A, Balling R, Barbacid M, Berns A, Bradley A, Brown S, Carmeliet P, Chambon P, Cox R, Davidson D, Davies K, Duboule D, Forejt J, Granucci F, Hastie N, de Angelis MH, Jackson I, Kioussis D, Kollias G, Lathrop M, Lendahl U, Malumbres M, von Melchner H, Müller W, Partanen J, Ricciardi-Castagnoli P, Rigby P, Rosen B, Rosenthal N, Skarnes B, Stewart AF, Thornton J, Tocchini-Valentini G, Wagner E, Wahli W, Wurst W. The European dimension for the mouse genome mutagenesis program. Nat Genet, 2004,36(9):925-927.
doi: 10.1038/ng0904-925 pmid: 15340424 |
[7] |
Austin CP, Battey JF, Bradley A, Bucan M, Capecchi M, Collins FS, Dove WF, Duyk G, Dymecki S, Eppig JT, Grieder FB, Heintz N, Hicks G, Insel TR, Joyner A, Koller BH, Lloyd KCK, Magnuson T, Moore MW, Nagy A, Pollock JD, Roses AD, Sands AT, Seed B, Skarnes WC, Snoddy J, Soriano P, Stewart DJ, Stewart F, Stillman B, Varmus H, Varticovski L, Verma IM, Vogt TF, von Melchner H, Witkowski J, Woychik RP, Wurst W, Yancopoulos GD, Young SG, Zambrowicz B. The knockout mouse project. Nat Genet, 2004,36(9):921-924.
doi: 10.1038/ng0904-921 pmid: 15340423 |
[8] |
Rozman J, Rathkolb B, Oestereicher MA, Schütt C, Ravindranath AC, Leuchtenberger S, Sharma S, Kistler M, Willershäuser M, Brommage R, Meehan TF, Mason J, Haselimashhadi H, Consortium I, Hough T, Mallon AM, Wells S, Santos L, Lelliott CJ, White JK, Sorg T, Champy MF, Bower LR, Reynolds CL, Flenniken AM, Murray SA, Nutter LMJ, Svenson KL, West D, Tocchini-Valentini GP, Beaudet AL, Bosch F, Braun RB, Dobbie MS, Gao X, Herault Y, Moshiri A, Moore BA, Kent Lloyd KC, McKerlie C, Masuya H, Tanaka N, Flicek P, Parkinson HE, Sedlacek R, Seong JK, Wang CL, Moore M, Brown SD, Tschöp MH, Wurst W, Klingenspor M, Wolf E, Beckers J, Machicao F, Peter A, Staiger H, Haring HU, Grallert H, Campillos M, Maier H, Fuchs H, Gailus-Durner V, Werner T, de Angelis MH. Identification of genetic elements in metabolism by high-throughput mouse phenotyping. Nat Commun, 2018,9(1):288.
doi: 10.1038/s41467-017-01995-2 pmid: 29348434 |
[9] |
Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, White JK, Meehan TF, Weninger WJ, Westerberg H, Adissu H, Baker CN, Bower L, Brown JM, Caddle LB, Chiani F, Clary D, Cleak J, Daly MJ, Denegre JM, Doe B, Dolan ME, Edie SM, Fuchs H, Gailus-Durner V, Galli A, Gambadoro A, Gallegos J, Guo SY, Horner NR, Hsu CW, Johnson SJ, Kalaga S, Keith LC, Lanoue L, Lawson TN, Lek M, Mark M, Marschall S, Mason J, McElwee ML, Newbigging S, Nutter LMJ, Peterson KA, Ramirez-Solis R, Rowland DJ, Ryder E, Samocha KE, Seavitt JR, Selloum M, Szoke-Kovacs Z, Tamura M, Trainor AG, Tudose I, Wakana S, Warren J, Wendling O, West DB, Wong L, Yoshiki A, International Mouse Phenotyping Consortium, Jackson Laboratory , Infrastructure Nationale Phenomin, Institut Clinique de la Souris (ICS), Charles River Laboratories, Harwell MRC, Toronto Centre for Phenogenomics, Wellcome Trust Sanger Institute, RIKEN BioResource Center, MacArthur DG, Tocchini-Valentini GP, Gao X, Flicek P, Bradley A, Skarnes WC, Justice MJ, Parkinson HE, Moore M, Wells S, Braun RE, Svenson KL, de Angelis MH, Herault Y, Mohun T, Mallon AM, Henkelman RM, Brown SDM, Adams DJ, Lloyd KCK, McKerlie C, Beaudet AL, Bućan M, Murray SA. High-throughput discovery of novel developmental phenotypes. Nature, 2016,537(7621):508-514.
doi: 10.1038/nature19356 pmid: 27626380 |
[10] |
Brown SDM, Chambon P, de Angelis MH, Eumorphia Consortium. EMPReSS: standardized phenotype screens for functional annotation of the mouse genome. Nat Genet, 2005,37(11):1155.
doi: 10.1038/ng1105-1155 pmid: 16254554 |
[11] |
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A. A conditional knockout resource for the genome-wide study of mouse gene function. Nature, 2011,474(7351):337-342.
doi: 10.1038/nature10163 pmid: 21677750 |
[12] |
Mouse megascience. Nature, 2010,465(7298):526.
doi: 10.1038/465526a pmid: 20520665 |
[13] | 魏强, 贺争鸣, 田克恭, 李红, 黄韧, 范薇, 屈霞琴 . GB 14922.2-2011 实验动物微生物学等级及监测. 2011. |
[14] | 岳秉飞, 高翔, 鲍世民, 张连峰, 邢瑞昌 . GB 14923-2010 实验动物哺乳类实验动物的遗传质量控制. 2010. |
[15] |
Zhang T, Xie PC, Dong YY, Liu ZW, Zhou F, Pan DJ, Huang ZY, Zhai QC, Gu Y, Wu QY, Tanaka N, Obata Y, Bradley A, Lelliott CJ, Sanger Institute Mouse Genetics Project, Nutter LMJ, McKerlie C, Flenniken AM, Champy MF, Sorg T, Herault Y, De Angelis MH, Durner VG, Mallon AM, Brown SDM, Meehan T, Parkinson HE, Smedley D, Lloyd KCK, Yan J, Gao X, Seong JK, Wang CKL, Sedlacek R, Liu Y, Rozman J, Yang L, Xu Y. High-throughput discovery of genetic determinants of circadian misalignment. PLoS Genet, 2020,16(1):e1008577.
doi: 10.1371/journal.pgen.1008577 pmid: 31929527 |
[16] |
Bowl MR, Simon MM, Ingham NJ, Greenaway S, Santos L, Cater H, Taylor S, Mason J, Kurbatova N, Pearson S, Bower LR, Clary DA, Meziane H, Reilly P, Minowa O, Kelsey L, International Mouse Phenotyping Consortium, Tocchini-Valentini GP, Gao X, Bradley A, Skarnes WC, Moore M, Beaudet AL, Justice MJ, Seavitt J, Dickinson ME, Wurst W, de Angelis MH, Herault Y, Wakana S, Nutter LMJ, Flenniken AM, McKerlie C, Murray SA, Svenson KL, Braun RE, West DB, Lloyd KCK, Adams DJ, White J, Karp N, Flicek P, Smedley D, Meehan TF, Parkinson HE, Teboul LM, Wells S, Steel KP, Mallon AM, Brown SDM. A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction. Nat Commun, 2017,8(1):886.
doi: 10.1038/s41467-017-00595-4 pmid: 29026089 |
[17] |
Moore BA, Leonard BC, Sebbag L, Edwards SG, Cooper A, Imai DM, Straiton E, Santos L, Reilly C, Griffey SM, Bower L, Clary D, Mason J, Roux MJ, Meziane H, Herault Y, International Mouse Phenotyping Consortium, McKerlie C, Flenniken AM, Nutter LMJ, Berberovic Z, Owen C, Newbigging S, Adissu H, Eskandarian M, Hsu CW, Kalaga S, Udensi U, Asomugha C, Bohat R, Gallegos JJ, Seavitt JR, Heaney JD, Beaudet AL, Dickinson ME, Justice MJ, Philip V, Kumar V, Svenson KL, Braun RE, Wells S, Cater H, Stewart M, Clementson-Mobbs S, Joynson R, Gao X, Suzuki T, Wakana S, Smedley D, Seong JK, Tocchini-Valentini G, Moore M, Fletcher C, Karp N, Ramirez-Solis R, White JK, de Angelis MH, Wurst W, Thomasy SM, Flicek P, Parkinson H, Brown SDM, Meehan TF, Nishina PM, Murray SA, Krebs MP, Mallon AM, Lloyd KCK, Murphy CJ, Moshiri A. Identification of genes required for eye development by high-throughput screening of mouse knockouts. Commun Biol, 2018,1:236.
doi: 10.1038/s42003-018-0226-0 pmid: 30588515 |
[18] |
Moore BA, Flenniken AM, Clary D, Moshiri AS, Nutter LMJ, Berberovic Z, Owen C, Newbigging S, Adissu H, Eskandarian M, McKerlie C, International Mouse Phenotyping Consortium, Thomasy SM, Lloyd KCK, Murphy CJ, Moshiri A. Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function. Sci Rep, 2019,9(1):11211.
doi: 10.1038/s41598-019-47286-2 pmid: 31371754 |
[1] | 陳吉芳,陳持平,蕭崇德. 台湾地区斑马鱼研究现况[J]. 遗传, 2012, 34(9): 1089-1096. |
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