??????????Nomenclature Guidelines for the Laboratory Mice

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??????????Nomenclature Guidelines for the
Laboratory Mice Rats

• ??? ???
• ?????? ??????
• ????????

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• Laboratory mouse
• Mus musculus musculus
• Mus musculus domesticus
• (Mus musculus molossinus, Mus musculus
  castaneus)
• Laboratory rat
• Rattus norvegicus

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• Rules for Nomenclature of Mouse
• and Rat StrainsLast updated Jan 2005
• http//www.informatics.jax.org/mgihome/nomen/stra
  ins.shtml
• Rules for Nomenclature of Genes, Genetic Markers,
  Alleles, and Mutations in Mouse and RatRevised
  Jan, 2004
• http//www.informatics.jax.org/mgihome/nomen/gene
  .shtml

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nomenclature gene protein
mouse ???????????,???????, ??????? Apc, adenomatosis polyposis coli ????????? ,???? APC
human ???????????,?????? APOA1, apolipoprotein A1 ????????? ,???? APOA1
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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

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Inbred Strains/????

• ??
• ?????? (brother x sister mating) 20 ?? 20
  ???,??????
• 20????????,????????????????????
• ??
• ????????????? (only 0.01 residual heterozygosity)
• ?????
• ????, ??????..etc.
• ??
• ??????(inbreeding depression) ???????????????
• Strain-specific characteristics
• ??

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Nomenclature of Inbred Strains

• ?????????,????????????????
• 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

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Substrains/??

• ??
• ???????????????????20?????,???????????????????????
  
• ???????????
• ?????????(residual heterozygosity)
• ?????
• ????
• ????(genetic drift)

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Nomenclature of Inbred Substrains
???? / ??(???)?????(Lab Code)
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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.shtm
  l
• JThe Jackson Laboratory
• NNational Institutes of Health
• CrlCharles River Laboratories
• RikThe Institute of Physical and Chemical
  Research (RIKEN)
• Narl National Applied Research Laboratories 
• (??????? ????????)

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Narl ?????????????????? 2005/4
?????? (Inbred strain rats)
?????? (Inbred strain Mice)
??? ??? ???
BALB/c BALB/cByJ BALB/cByJNarl
C3H C3H/HeNCr C3H/HeNCrNarl
C57BL/6 C57BL/6J C57BL/6JNarl
CBA CBA/CaJ CBA/CaJNarl
DBA/2 DBA/2J DBA/2JNarl
FVB FVB/NJ FVB/NJNarl
??? ??? ???
BN BN/SsN BN/SsNNarl
F344 F344/N F344/NNarl
LEW LEW/SsN LEW/SsNNarl
SHR SHR/NCrl SHR/NCrlNarl
WKY WKY/NCrl WKY/NCrlNarl
?????? (Outbred stock rats)
 ?????? (Outbred stock mouse)
??? ???
SD NarlSD
Wistar NarlWistar
Long Evans NarlLE
??? ???
ICR NarlICR
????????? (Congenic inbred strain nude mouse)
??? ??? ???
BALB/c-nu BALB/cAnNCrl-Foxn1nu BALB/cAnN.Cg-Foxn1nu/CrlNarl
??????? (Outbred stock mouse)
??? ??? ???
ICR-nu ICR-nu/nu NarlICR-Foxn1nu
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Nomenclature of Inbred Substrains (continued)
????????????????,??????(Lab Code)????????????
C57BL/6JOlaHsdEi
C57BL parent strain designation
6JOlaHsdEi substrain designation
6 line number J laboratory
code Ola laboratory code
Hsd laboratory code Ei
Laboratory code
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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
???,NCI, Amsterdam
1961, Bailey, NIH
1935, F26, Snell moved to JAX
1967, F99, Bailey(By), JAX
1973, CIEA, Japan
1935, F?, Andervont (An), NIH
1975, F136, JAX
1989, CLEA, Japan
1951, F72, NIH
BALB/cAJcl
BALB/cAnN
BALB/cByJ
2001, F?, Narl
1995, F?, Narl
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Case Study
Substrain Animal Provider Genotype Phenotype
BALB/cByJ The Jackson Laboratory A 278 bps deletion of the acyl-Coenzyme A dehydrogenase, short chain, (Acads ) locus severe organic aciduria hypoglycemia and elevated urinary and muscle butyryl carnitine 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.
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F1 Hybrids/?????

• ??
• ?????????,??????????????
• ??
• ?????????????, F1 hybrid??????????????????????(iso
  genicity)
• ??????(hybrid vigor) ,??????????????
• ???????????????
• ??
• F1??????????,???????????????F2 hybrid,??????????

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F1 hybrid??????????????? ???????(isogenicity)
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Nomenclature of F1 hybrid
????????????F1
??????
D2B6F1 Mouse that is the offspring of a DBA/2
mother and C57BL/6 father
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Nomenclature of F1 hybrid
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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
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Recombinant Inbred Strains/??????

• ??
• ???????????,?????F1??????????????20???,??????????
  ???
• ??
• Segregation and linkage analysis
• Identify quantitative trait loci (QTLs)
• Create new models

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Nomenclature of Recombinant Inbred Strains
?????? X ????????
??????
CXB61 RI mouse strain derived from a cross of
BALB/c x C57BL/6, line 1
B6XC5 RI mouse strain derived from a cross of
C57BL/6 x BALB/c, line 5
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Congenic Inbred Strains/??????

• ??
• ??????????????????(donor strain)???????????(recipi
  ent strain background strain)?,???(backcross)???/
  ??(backcross-intercross) 10 ???,??????????????????
  
• ????????????????????????????????,?????,???????????
  ???????
• 5?Nlt10 generations are considered incipient
  congenic

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A congenic strain is formed by backcrossing a
locus of interest onto an inbred mouse strain for
10 or more generations.
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Congenic inbred strain
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Congenic inbred strain
??????????,??????????,??????????????????
BALB/c (/) ? A (nu/nu) recipient strain
donor strain
Outcross
/nu
/nu ? /nu (or /nu ? nu/nu)
Incross, Intercrosss
/, /nu, nu/nu
Test cross
BALB/c (/) ? BALB/c (nu/nu)
Backcross
Incross, Intercross
/nu
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Nomenclature of Congenic Inbred Strains
Recipient Strain.Donor Strain ? ??
??????

• ???????????????donor strain

B6.AKR-H2k recipient strainC57BL/6J
donor strainAKR B6.129P2-Tcrbtm1Mom
recipient strain C57BL/6J donor strain
129P2 via E14TG2a ES cell line

• ?donor strain ??inbred,???????????????,? Cg ???

B6.Cg-Tcrbtm1Mom
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Nomenclature of Congenic Inbred Strains
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Common name Nude SCID
characteristics The homozygous for the nude spontaneous mutation are abnormal hair growth and defective development of the thymic epithelium, lack T cells and suffer from a lack of cell-mediated immunity. Mice homozygous for the SCID spontaneous mutation are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironment.
Former symbol Nu Hfh11nu (Changed 1995) scid
Gene symbol Foxn1nu (Changed 2000) Prkdcscid (Changed 1997)
Gene name forkhead box N1 protein kinase, DNA activated, catalytic polypeptide
Strains (i.e.) CByJ.Cg-Foxn1nu/J B6.Cg-Foxn1nu/J NOD.CB17-Prkdcscid/J B6.CB17-Prkdcscid/SzJ
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Coisogenic Inbred Strains/????????

• ??
• ???????????????? (????targeted mutation)
  ,?????,??/??????????????
• 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

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Nomenclature of Coisogenic Inbred Strains
??/?? ? ??(????)

• 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.

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Genetically Engineered strains

• Transgenesis
• Adding new genetic material
• Homologous Recombination
• Targeting a specific gene using ES cells
• Random Mutagenesis
• chemicals or irradiation

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Nomenclature for Transgenics
??(/??) ? Tg(??)??Lab code
FVB/NCrl Tg(Pgk1-EGFP)3Narl

• FVB/NCrlgenetic background
• TgTransgenic
• (Pgk1-EGFP)insert designation
• promoterPhosphoglycerate kinase 1
  (recommended)
• geneenhanced green fluorescent
• protein
• 3laboratory assigned number (founder number)
• NarlLab code

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Nomenclature for Targeted Mutations
??(/??)??? tmserial numberLab Code

• ? tm ?? targeted mutation
• Serial number ??????????
• Lab Code ??????????

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Outbred stocks/????

• ??
• ?????????,??????????????,?????????,???????????(gen
  etically heterogeneous)

• ????
• ?????? (circular pair mating)
• ???? (circular mating)

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Nomenclature of Outbred stocks
Lab codestock symbol
CrlCD-1(Icr) the ICR outbred mice that are
breeding at Charles River Laboratory HsdLE the
Long-Evans outbred rats that are breeding at
Harlan Sprague Dawley
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RecommendationsBanbury 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, 19755-759.

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.
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RecommendationsTo 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

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Mouse Genome Informatics (MGI) http//www.informa
tics.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/
??????? ???????? http//www.nlac.org.tw/
??????? http//las.nhri.org.tw/
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Thanks!