() Guide for the Care and Use of Laboratory Animals.

Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS

() Guide for the Care and Use of Laboratory Animals.

Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS

() () ()

mouse inbred: C57BL,C3H,BALB/c,DBA/2, CBA,A,AKR, NZB, NZW, SJL outbred:ICR, Swiss Webster, ddy

rat inbred:F344, LEW, BN, SHR,WKY, DA, PVG, WAG, ACI, WFoutbred: Sprague-Dawley, Wistar,

Long-Evans hamster Syrian hamster, Chinese

hamster,European hamster

gerbil Mongolian gerbil

guinea pig inbred:Strain 2, Strain 13outbred:Duncan-Hartley, Hartley

rabbit New Zealand White Dutch

dog Beagle, Grey houndMixed breed(Mongrel)

cat Domestic short hairMixed breed

nonhman-primate

() () ()

http://www.cix.co.uk/~embra/armyths.html50.1Total

Estimated on the side of caution10others

Report of the Australian Senate Select Committee on Animal Welfare: Animal Experimentation (1989)

0.75Australia

Swiss Federal Office of Veterinary Care (1993)0.86Switzerland

Canadian Council on Animal Care (1995) Resource 182.1Canada

Estimated on the side of caution2.5Japan

Commission of the European Communities (1994)11.8EU*

US Congress Office of Technology Assessment (1986)22.0USA

()

0

20

40

60

80

100

120

140

160

180

200Number of Animal Sales (thousand)

0

5000

10000

15000

20000

25000

30000

35000

40000

Sales Amount in NTD

Number of Animal Sales Sales Amount in NTD

Number of Animal Sales 12.6 37.8 53 71 90.5 124 128 142 158 183 168

Sales Amount in NTD 1454 5209 7005 8836 1110 1608 1641 1859 2400 3350 3041

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

919293() ()

12.150.010.053101.4121.5693

22.650.010.052.1109.1138.492

20.84.60.010.051.973.2100.591

*2

*1

,...AIDS

1990s

...

1980s

..1970s

...

1960s

.....

1950s

..1940s

.1930s

.1920s

.1900s

25 25

20 20

30 30

10 10

15 15

1. (Induced or experimental models)alloxane

2. (Spontaneous or natural models)

3. (Negative or non reactive models)

4. (Orphan models)(Marek's disease)(BSE)

:

Homology

Analogy

Wistar BB

1.

2.

3.

4.

5.

6.

7.

1. 2. 3. 4. 5.

6.

1.

(1) (2) (3) (4) (5) (6) (7) (8) (9)

9.(1) (2) (3)

10.

2. 3. 4. 5. 6. 7. 8.

11.

1.

2.

3.

4.

1.

(1) (prospective)(retrospective)

(2)

(3) 2.5060561020030045520

3.

1.(prototype)

2.

1.

(1) (2) (3) (4) (5) (6) (7)

2.(1)

(2)

87%

0.3%0.2%0.4%

1.7%

9%

2.4%

RatMice

C57BL/6

BALB/c

MICE

Sprague-Dawley

SHR

Rats

(gerbil)

(hamster)

Beagle dog

1.2.3.Arthritis models

4.Nephritis5.Diabetes mellitus6.(Viral hepatitis)7.

(Atherosclerosis)8.(Cardiomyopathy)

9.(Myocardial ischemia)

10.(Cancer research)11.

(Transgenic and gene knock-out animals)

12.: (nuclear transfer),

13.(Animal models in toxicity testing)

(1)

(2): Spontaneous hypertension rats (SHR)

polygenic

1.

WKY

SHR/N

2. (1)(cyclosporin)

(2) a.Nude(nu): T b.Nude(rnu): T c. Beige (bg): d. X-linked immunodeficiency (xid)B e. severe combined immunodeficiency (scid)

TB f. non- obese diabetic (nod) : g.nod-scid T B NK macrophage

NOD-SCID

SCID mice

Nude mice

h. Osteopetrosis (op)

i. Multiple mutant strainsscid-beigeTBNKnude-beigeTNKbeige-nude-xidTBNK nod-scidTBNK

i. Chediak-Hagashi syndromeDefect in sorting pathway of secretory

lysosome in immune cells and melanocytesFailure to fuse lysosome properly with phagosomeImmunodeficiency (impaired intracellular killing)

and albinism

3.Arthritis models

Antigen induced (in complete Freunds adjuvant)- albumin, - type II collagen (collagen induced arthritis, CIA)- aggrecan (human cartilage proteoglycan)- peptidoglycans from Streptococcus- heat killed Mycobacterium

Antibody induced-type II collagen-glucose-6-phosposphate-isomerase (GPI)

TNF- Transgenic miceK/BxN (KRN, NOD hybrid): antibody to GPIMRL/lC57BLNZB

(1)lpr (lymphoproliferation)(2)ank (progressive ankylosis)(3)moblo (mottled-blotchy)

4.Nephritis

(1)ddy(2)(NZB NZW)F1

NZW/LacJ , NZB/B1NJ

5.Diabetes mellitusHypoinsulinemia (juvenile-onset,

insulin dependent, ketosis prone)(1)BBWistar(2)

(3)13

(4) Non-obese diabetic (NOD)mice autoimmune/Th1

(5) Streptozocin or alloxane-induced(6) C57BL/6-Ins2Akita/J: congenic,

insulin II gene( Ins2)

Non-obese diabetic

Chinese hamster

Hyperinsulinemia (maturity-onset, nonketotic, noninsulin-dependent, obesity)

(1): KK miceC57BL/6J-Lepob/Lepob : ZDF/Gmi-fa (Zucker diabetic fatty rat)

WDF/Ta-fa (Wistar diabetic fatty rat)

Lepob/Lepobmutation in the gene for leptin (hormone)

(2)(Leprdb)C57BL/KsJ-Leprdb/Leprdb

Leprdb/Leprdb mutation in the gene for leptin receptor(hypothalamus)

Relation among weight, leptin, NPY(neuropeptide Y), and eatingOrdinarily, high levels of body fat produce leptin, which inhibits eating.

Obese mice fail to produce leptin. Obese humans produce leptin but fail to respond to it.

Non-obese diabetic

129J-Leprdb/LeprdbC57BL/KsJ-Leprdb/Leprdb

B6.V-Lepob/J

:

C57BLKS/J-m +/+ db (repulsion ) (intercross)

m +/+ db x m +/+ db

m + /m + m + / + db + db/+ db1 2 1

( ) ( )

, (),

6.(Viral hepatitis) B (Marmota monax): B

Woodchuck hepatitis virus (WHV): hepadnavirusSimilarity between WHV and HHVChronic liver disease and primary hepatocelluar carcinoma (HCC)

LEC rats (derived from Long-Evans):40%: Fulminant hepatitis 60%: Chronic hepatitis and cancer

(woodchuck) (woodchuck)

7.(Atherosclerosis) ()

Carneau pigeons(atherogenic)

(Marek's disease)

(hypercholesterolemia)(Lab Anim Sci 43:575,1993)

(hypertriglyceridemia)

Hamster Good model for

Total Cholesterol/high density Cholesterol- Hamster is close to human

Human: High density=180 low density = 50Mice: high density = 50 low density > 100(mice is different from human, On the other hand, hamster is similar to human: high densityis higher than low density cholesterol)

8.(Cardiomyopathy)Dilated cardiomyopathy: TO-2 hamsterHypertrophic cardiomyopathy : BIO14.6

9.(Myocardial ischemia)

C57BL/6- Xintm

Hamster BIO14.6

10.(Cancer research)

(Xenograft)

SCID E-B

(Burkitt's lymphoma) AKR

11.(Transgenic and gene knock-out animals)

Cancer research- C57BL/6J-Trp53 tm1Tyj

(Trp:transformation related protein)- 129S1/SvImJ-Rb1 tm1Tyj- H-Ras K-Ras transgeneB6;SJL-Tg(WapHRAS)69Lln Chr YSJL/J

Cystic fibrosisB6.129P2-Cftrtm1Unc/J(cystic fibrosis transmembrane conductance regulator)

AtherosclerosisC57BL/6J-Apoe tm1Unc

Diabetes

NOD-Tg(CD90CD90.1)

Th1 Th2 double transgene

NOD.129S6(B6)-Cd4tm1Knw/DvsJ (resistant)

Anti-inflammation

NOD-Tg (PGK-DcR3)

(decoy receptor 3)

12.: (nuclear transfer),

(Dolly sheep)

(Wilmut et al., 1997)

(Investigational New Drug)

(New Drug Application)

()

(Investigational New Drug)

13.(Animal models in toxicity testing)

(1) 24

(2) 0.1ml0.1

(discharge)(3) )

(4)(GPM)

(5)

SD

ICR mice

Beagle dogBeagle dog

(6)

(7) 18-24

(8)

Animal models for dental diseases

High carbohydrate diet containing high amount of P, Ca, Mg

Rats Calculus

Biglycan (Bgn) deficient miceOvariectomized rats

MiceRats

Osteoporosis(Dental implantology)

Streptococcus mutansStreptococcus sobrinusStreptococcus gordoniiActinobacillus+ sucrose+ host cariogenic diet

Rats(Mice)

Dental caries

CyclosporinRats (SD) Gingival overgrowth

Porphyromonas gingivalisDog Rats (F344)HamsterCat

Periodontal diseases(periodontitis)

Remarks Animal model Diseases

1.Plenty Information : anatomy, histology, flora, biochemistry of oral tissues etc.

2.Susceptible to every major oral diseases in humans

3. Adapt well to changes in environment, diet or husbandry

4. Easy to manipulate: saliva & blood collection, administration of test agents, dietary manipulation

5. Costs are low

Rats - Good animal model for dental diseases

Sectioned rat molars with carious lesions

Carious areas on the surface of mandibular molars

ENU (E-ethyl-N-nitrosourea) -

-

Laboratory Animal Strains

C3H/HeNCrlNarl C57BL/6JNarl BALB/cByJNarl Narl:Swiss Webster4Mice

2. Germ-FreeNarl:Syrian hamster1Hamster

BN/SsNNarl F344/NNarl LEW/SsNNarlSHR/NCrlNarl WKY/NCrlNarl,

Narl:LE Narl:SD Narl:Wistar8Rat

BALB/cByJNarl BALB/cAnNNarlC57BL/6JNarl CBA/CaJNarl

DBA/2JNarl FVB/NJNarl C3H/HeNcrNarl BALB/cAnN.Cg-Foxn1nu/CrlNarl

Narl:ICR Narl:ICR-Foxn1nu

10Mouse

1. SPF

Strain/StockNumberLaboratory Animal

The New Strains to Breed

The goal is to improve the quality and diversity of laboratory animal stains including the rare strains.

Six stains in 2005:NOD.CB17- Prkdcscid/JNOD/LtJC.B17/Icr-scidBKS.Cg-m +/+ Leprdb/JB6.V-Lepob/J129X1/SvJ

Two strains in 2006:KK/AyBALB/cJ

. 2003