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
象
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
同
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!