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實驗大、小鼠命名原則

Nomenclature Guidelines for

the Laboratory Mice & Rats





吳希天 周傳凱

國立嘉義大學 精緻農業學系

國家實驗動物中心

 Laboratory mouse

Mus musculus musculus

Mus musculus domesticus

(Mus musculus molossinus, Mus musculus

castaneus)





 Laboratory rat

Rattus norvegicus

for Nomenclature of Mouse

 Rules

and Rat Strains

Last updated: Jan 2005

http://www.informatics.jax.org/mgihome/nomen/strains.shtml





 Rulesfor Nomenclature of Genes,

Genetic Markers, Alleles, and

Mutations in Mouse and Rat

Revised: Jan, 2004



http://www.informatics.jax.org/mgihome/nomen/gene.shtml

nomenclature gene protein



基因符號以斜體英文字母, 蛋白質符號全部大寫

第一個字母大寫, ,不需斜體

第二個以後小寫

mouse

Apc, APC

adenomatosis

polyposis coli

基因符號以斜體英文字母, 蛋白質符號全部大寫

所有字母大寫 ,不需斜體

human

APOA1, APOA1

apolipoprotein A1

Categories of characterized animals

 Inbred strains

 Substrains

 Hybrids

 F1 Hybrids

 Recombinant Inbred Strains

 Congenic Inbred Strains

 Mixed Inbred Strains

 Coisogenic Inbred Strains

 Genetically Engineered strains

 Transgenic

 Targeted mutations (“knockouts” or “knockins”)

 Consomic Strains, Segregating Inbred Strains &

Conplastic Strains

 Outbred Stocks

Inbred Strains/近親品系

 定義

兄妹近親交配 (brother x sister mating) 20 代或 20 代以上,且在此品系之

20代或接續的世代中,每一個個體皆可追溯自單一個來源之祖先對。





 優點

 遺傳性狀及表現性狀具一致性 (only 0.01 residual heterozygosity)

 品系特殊性

 性狀穩定, 國際流通性佳…..etc.





 缺點

 近親抑制現象(inbreeding depression) 如體型小、低繁殖率、生命期短等

 Strain-specific characteristics

 昂貴

Nomenclature of Inbred Strains



 具簡潔獨特性之符號,以英文大寫字母或字母連結數字表示

 based on coat color

DBA (Dilute Brown nonAgouti,

first inbred mouse)

 based on origin

NZW (New Zealand White)

 based on phenotype

NOD (Non-Obese Diabetic)

 others

BALB/c, C57BL, 129

Substrains/支系



 定義

 近親品系之繁殖族群與其共同祖先分離超過20個世代以上,

或族群之維持完全獨立於其原始品系之外而形成支系



 不同族群間遺傳性狀歧異

 分離時殘留的雜合子(residual heterozygosity)

 自發性突變

 遺傳污染

 遺傳漂流(genetic drift)

Nomenclature of Inbred Substrains



[原始品系] / [序號(可省略)][實驗室編碼(Lab Code)]

A Laboratory Code

 The Institute for Laboratory Animal Research (ILAR) maintains the

International Laboratory Code Registry (Lab Codes).

 The purpose of this database is to accurately identify at which

laboratory or institution a strain of animals was bred and maintained.

 Environmental factors can affect the characteristics of a strain, it is

important to document where a strain originated



http://dels.nas.edu/ilar_n/ilarhome/labcode.shtml



 J:The Jackson Laboratory

 N:National Institutes of Health

 Crl:Charles River Laboratories

 Rik:The Institute of Physical and Chemical Research (RIKEN)

 Narl :National Applied Research Laboratories

(國家實驗研究院 國家實驗動物中心)

+ Narl 國家實驗動物中心大、小鼠品系『正名』 2005/4

近親品系小鼠 (Inbred strain Mice): 近親品系大鼠 (Inbred strain rats):

品系名 原命名 新命名 品系名 原命名 新命名



BALB/c BALB/cByJ BALB/cByJNarl BN BN/SsN BN/SsNNarl

C3H C3H/HeNCr C3H/HeNCrNarl F344 F344/N F344/NNarl

C57BL/6 C57BL/6J C57BL/6JNarl LEW LEW/SsN LEW/SsNNarl

CBA CBA/CaJ CBA/CaJNarl SHR SHR/NCrl SHR/NCrlNarl

DBA/2 DBA/2J DBA/2JNarl WKY WKY/NCrl WKY/NCrlNarl

FVB FVB/NJ FVB/NJNarl

遠交品種大鼠 (Outbred stock rats):

遠交品種小鼠 (Outbred stock mouse): 品種名 新命名

品種名 新命名

SD Narl:SD

ICR Narl:ICR Wistar Narl:Wistar

Long Evans Narl:LE

同源近親品系裸小鼠 (Congenic inbred strain nude mouse):

品系名 原命名 新命名



BALB/c-nu BALB/cAnNCrl-Foxn1nu BALB/cAnN.Cg-Foxn1nu/CrlNarl



遠交品種裸小鼠 (Outbred stock mouse):

品種名 原命名 新命名



ICR-nu ICR-nu/nu Narl:ICR-Foxn1nu

nlac

Nomenclature of Inbred Substrains

(continued)







由於遺傳的變異隨時間的演進而出現,故實驗室編碼

(Lab Code)應隨品系的轉移而累加於後





C57BL/6JOlaHsdEi

C57BL = parent strain designation

6JOlaHsdEi = substrain designation

6 = line number

J = laboratory code

Ola = laboratory code

Hsd = laboratory code

Ei = Laboratory code

The Genealogy of BALB/c Strain

1913, Halsey J. Bagg, albino



1923, Little & MacDowell, strat inbreeding



1927, F12, Muller, University of Texas



1932, Snell (added the /c), University of Texas



1961, Bailey, NIH 1935, F26, Snell moved to JAX ???,NCI, Amsterdam





1967, F99, Bailey(By), JAX 1973, CIEA, Japan

1935, F?, Andervont (An), NIH



1975, F136, JAX 1989, CLEA, Japan

1951, F72, NIH





BALB/cByJ BALB/cAnN BALB/cAJcl





1995, F?, Narl 2001, F?, Narl

nlac

Case Study



Animal

Substrain Genotype Phenotype

Provider



 severe organic aciduria

A 278 bps deletion of  hypoglycemia and

The Jackson the acyl-Coenzyme A elevated urinary and

BALB/cByJ

Laboratory dehydrogenase, short muscle butyryl carnitine

chain, (Acads ) locus concentrations

(after 18 hrs fasting)





BALB/cAnN The NIH Locus intact Normal





BALB/cAJcl CLEA, Japan Locus intact Normal



Reference: Armstrong DL, Masiowski ML, Wood PA. Pathologic characterization of short-chain acyl-CoA

dehydrogenase deficiency in BALB/cByJ mice. Am J Med Genet 1993 ;47(6):884-92.

F1 Hybrids/第一代雜交

 定義

兩個不同近親品系鼠,經過雜交後所出生之第一代小鼠



 優點

 遺傳性狀及表現性狀具一致性, F1 hybrid在每個基因座上都

有與父系或母系相同的遺傳基因(isogenicity)

 具有雜交優勢(hybrid vigor) ,卻沒有近親品系之近親抑制現



 可接受來自父系或母系的組織移植





 缺點

 F1不能再當種畜進行繁殖,因其結果會產生許多不同基因型之

F2 hybrid,而失去其一致性之特性

F1 hybrid在每個基因座上都有與父系或母系

相同的遺傳基因(isogenicity)

Nomenclature of F1 hybrid





[母系親代品系*][父系親代品系*]F1



*英文大寫縮寫







D2B6F1

Mouse that is the offspring of a

DBA/2 mother and C57BL/6 father

Nomenclature of F1 hybrid

Standard Abbreviations Used in Hybrid Names



Abbreviation Strain Abbreviation Strain

129P 129P3/J L C57L/J

129S 129S1/SvImJ CBACa CBA/CaGnLe

AHe A/HeJ CB CBA

A A/J C3 C3H/HeJ

AK AKR/J C3Fe C3HeB/FeJ

CBy BALB/cByJ D1 DBA/1J

C BALB/cJ D2 DBA/2J

B C57BL NZB NZB/BlNJ

B6 C57BL/6J NZW NZW/LacJ

B10 C57BL/10J SJL or J SJL/J

BR C57BR/cdJ SW SWR/J

Recombinant Inbred Strains/重組近親品系



 定義

兩個已知的近親品系雜交,由所產生的F1雜交鼠實施連

續的近親兄妹交配20代以上,形成一系列或一組的近親

品系



 應用

 Segregation and linkage analysis

 Identify quantitative trait loci (QTL’s)

 Create new models

Nomenclature of

Recombinant Inbred Strains





[母系親代品系*] X [父系親代品系*][序號]

*英文大寫縮寫







CXB61 B6XC5

RI mouse strain derived RI mouse strain derived

from a cross of from a cross of

BALB/c x C57BL/6, C57BL/6 x BALB/c,

line 1 line 5

Congenic Inbred Strains/同源近親品系

 定義

 某外源基因和連帶的一段染色體由他品系(donor strain)以雜交

方式導入受領品系(recipient strain; background strain)內,經

回交(backcross)或回交/互交(backcross-intercross) 10 代以上

,並經適當的遺傳標記篩選所育成之新品系

 同源近親品系除了在同一基因區之某幾對基因與原來之近親品系

有所不同,保持分離外,其在遺傳上之特性與原品系幾乎完全相



 5≦N<10 generations are considered incipient congenic

A congenic strain is formed by backcrossing a locus of interest

onto an inbred mouse strain for 10 or more generations.

Congenic inbred strain

Congenic inbred strain

以裸鼠之繁殖育種為例,由表型即可判斷基因型,且當雌鼠為隱性純合子時無法哺育子代。



BALB/c (+/+)  A (nu/nu) Outcross

recipient strain donor strain





+/nu



+/nu  +/nu (or +/nu  nu/nu)

Incross,

+/+, +/nu, nu/nu Intercrosss



Test cross





BALB/c (+/+)  BALB/c (nu/nu) Backcross



Incross,

+/nu Intercross

Nomenclature of Congenic Inbred Strains



[Recipient Strain*].[Donor Strain*] ▬ [基因]

*英文大寫縮寫



 所導入之基因及其對偶基因來自於donor strain



B6.AKR-H2k

recipient strain:C57BL/6J

donor strain:AKR



B6.129P2-Tcrbtm1Mom

recipient strain :C57BL/6J

donor strain :129P2 via E14TG2a ES cell line



 若donor strain 不是inbred,而是雜交、遺傳背景混雜或未知時,

以“ Cg ”表示之



B6.Cg-Tcrbtm1Mom

Nomenclature of Congenic Inbred Strains

Common name Nude SCID

Mice homozygous for the SCID

The homozygous for the nude

spontaneous mutation are

spontaneous mutation are

characterized by an absence of

abnormal hair growth and

functional T cells and B cells,

characteristics defective development of the

lymphopenia,

thymic epithelium, lack T cells

hypogammaglobulinemia, and a

and suffer from a lack of cell-

normal hematopoietic

mediated immunity.

microenvironment.



Nu

Former symbol scid

Hfh11nu (Changed: 1995)



Gene symbol Foxn1nu (Changed: 2000) Prkdcscid (Changed: 1997)



protein kinase, DNA

Gene name forkhead box N1 activated, catalytic

polypeptide



CByJ.Cg-Foxn1nu/J NOD.CB17-Prkdcscid/J

Strains (i.e.)

B6.Cg-Foxn1nu/J B6.CB17-Prkdcscid/SzJ

Coisogenic Inbred Strains/突變同源近親品系



 定義

同一近親品系內某一基因座發生改變 (如突變、targeted

mutation…) ,而利用回交,回交/互交等方式所保留下來

之新品系





 spontaneous mutation

 targeted mutations strains are crossed to, and

maintained, on the same ES cells background

substrain

 chemically or radiation induced mutants on an

inbred background

Nomenclature of Coisogenic Inbred Strains



[品系]/[旁系] ▬ [基因(對偶基因)]



Spontaneous or Random Mutation

C3H/HeJ-md2J

The mahoganoid 2J mutation in the C3H/HeJ strain



Targeted Mutation

129S7/SvEvBrd-Fyntm1Sor



A targeted mutation of the Fyn gene was produced using the

AB1 ES cell line derived from 129S7/SvEvBrd. Chimeric

animals were mated to 129S7/SvEvBrd and the allele

subsequently maintained on this coisogenic strain.

Genetically Engineered strains



 Transgenesis

Adding new genetic material







 Homologous Recombination

Targeting a specific gene using ES cells







 Random Mutagenesis

chemicals or irradiation

A→G

Nomenclature for Transgenics

品系(/旁系) ▬ Tg[(基因)][序號][Lab code]



FVB/NCrl – Tg(Pgk1-EGFP)3Narl

 FVB/NCrl:genetic background

 Tg:Transgenic

 (Pgk1-EGFP):insert designation

 promoter:Phosphoglycerate kinase 1

(recommended)

 gene:enhanced green fluorescent

protein

 3:laboratory assigned number (founder number)

 Narl:Lab code

Nomenclature for Targeted Mutations



品系(/旁系)▬基因 tm[serial number][Lab Code]

 以 tm 代表 targeted mutation

 Serial number :來自於實驗室原始編號

 Lab Code :突變株所來自之實驗室



knock-out 129X1-Cftrtm1Unc



the first targeted mutation of the cystic fibrosis transmembrane regulator

(Cftr) gene at 129X1, produced at the University of North Carolina



knock-in 129X1-En1tm1(Otx2)Wrst

the coding region of En1 was replaced by the Otx2 gene, originating from

the W. Wurst laboratory

Outbred stocks/遠親品種



 定義

 指封閉族群內之雜交,其結果可維持較大的遺傳變

異性,減少近親係數的比例,亦即維持族群中之異

質性(genetically heterogeneous)







 配種方式

 環型成對交配 (circular pair mating)

 環型交配 (circular mating)

Nomenclature of Outbred stocks





Lab code:stock symbol





Crl:CD-1®(Icr)

the ICR outbred mice that are breeding at

Charles River Laboratory





Hsd:LE

the Long-Evans outbred rats that are breeding

at Harlan Sprague Dawley

Recommendations

Banbury Conference* Guidelines



 Published reports must include a detailed description of

genetic background of the mice studied that is

sufficient enough to allow replication of the study

 The genetic background chosen for the studies should

not be so complex as to preclude replication

 Use of common or standardized genetic background

would facilitate comparison of experimental results

among laboratories

Neuron 1997, 19:755-759.





*The Banbury Center is the small conference center at Cold Spring Harbor Laboratory.

The meetings, for groups of between 30 and 40 scientists, are recognized

internationally as being amongst the world's best discussion workshops for topics in

molecular biology, molecular genetics and science policy.

Recommendations

To Obtain Optimal Mouse Model



 Select both the optimal genetic background as

well as the genetically modified gene.

 Analyze mutation on 4 or 5 different inbred

backgrounds

 If choose hybrid background, make sure you

consider genes segregating independently of

your modified gene

 Pay attention to environmental factors (health

status, diet, light cycle, animal husbandry) that

may affect phenotype

Mouse Genome Informatics (MGI)

http://www.informatics.jax.org/





http://www.ncbi.nlm.nih.gov/genome/guide/mouse/



The Rat Genome Database (RGD)

http://rgd.mcw.edu/







http://www.ncbi.nlm.nih.gov/genome/guide/rat/





國家實驗研究院 國家實驗動物中心

nlac

http://www.nlac.org.tw/





實驗動物資訊網

http://las.nhri.org.tw/

Thanks!


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