疾病動物模式 - lac.nhri.org.twlac.nhri.org.tw/files/slides/950315.pdf · •...
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() 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
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() () ()
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
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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
() () ()
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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
()
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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
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919293() ()
12.150.010.053101.4121.5693
22.650.010.052.1109.1138.492
20.84.60.010.051.973.2100.591
*2
*1
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,...AIDS
1990s
...
1980s
..1970s
...
1960s
.....
1950s
..1940s
.1930s
.1920s
.1900s
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25 25
20 20
30 30
10 10
15 15
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1. (Induced or experimental models)alloxane
2. (Spontaneous or natural models)
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3. (Negative or non reactive models)
4. (Orphan models)(Marek's disease)(BSE)
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:
Homology
Analogy
Wistar BB
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1.
2.
3.
4.
5.
6.
7.
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1. 2. 3. 4. 5.
6.
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1.
(1) (2) (3) (4) (5) (6) (7) (8) (9)
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9.(1) (2) (3)
10.
2. 3. 4. 5. 6. 7. 8.
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11.
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1.
2.
3.
4.
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1.
(1) (prospective)(retrospective)
(2)
(3) 2.5060561020030045520
3.
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1.(prototype)
2.
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1.
(1) (2) (3) (4) (5) (6) (7)
2.(1)
(2)
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87%
0.3%0.2%0.4%
1.7%
9%
2.4%
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RatMice
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C57BL/6
BALB/c
MICE
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Sprague-Dawley
SHR
Rats
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(gerbil)
(hamster)
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Beagle dog
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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)
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(1)
(2): Spontaneous hypertension rats (SHR)
polygenic
1.
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WKY
SHR/N
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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
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NOD-SCID
SCID mice
Nude mice
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h. Osteopetrosis (op)
i. Multiple mutant strainsscid-beigeTBNKnude-beigeTNKbeige-nude-xidTBNK nod-scidTBNK
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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
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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)
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TNF- Transgenic miceK/BxN (KRN, NOD hybrid): antibody to GPIMRL/lC57BLNZB
(1)lpr (lymphoproliferation)(2)ank (progressive ankylosis)(3)moblo (mottled-blotchy)
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4.Nephritis
(1)ddy(2)(NZB NZW)F1
NZW/LacJ , NZB/B1NJ
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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)
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Non-obese diabetic
Chinese hamster
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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)
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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.
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Non-obese diabetic
129J-Leprdb/LeprdbC57BL/KsJ-Leprdb/Leprdb
B6.V-Lepob/J
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:
C57BLKS/J-m +/+ db (repulsion ) (intercross)
m +/+ db x m +/+ db
m + /m + m + / + db + db/+ db1 2 1
( ) ( )
, (),
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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)
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7.(Atherosclerosis) ()
Carneau pigeons(atherogenic)
(Marek's disease)
(hypercholesterolemia)(Lab Anim Sci 43:575,1993)
(hypertriglyceridemia)
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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)
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8.(Cardiomyopathy)Dilated cardiomyopathy: TO-2 hamsterHypertrophic cardiomyopathy : BIO14.6
9.(Myocardial ischemia)
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C57BL/6- Xintm
Hamster BIO14.6
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10.(Cancer research)
(Xenograft)
SCID E-B
(Burkitt's lymphoma) AKR
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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)
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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)
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12.: (nuclear transfer),
(Dolly sheep)
(Wilmut et al., 1997)
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(Investigational New Drug)
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(New Drug Application)
()
(Investigational New Drug)
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13.(Animal models in toxicity testing)
(1) 24
(2) 0.1ml0.1
(discharge)(3) )
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(4)(GPM)
(5)
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SD
ICR mice
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Beagle dogBeagle dog
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(6)
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(7) 18-24
(8)
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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
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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
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Sectioned rat molars with carious lesions
Carious areas on the surface of mandibular molars
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ENU (E-ethyl-N-nitrosourea) -
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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
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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
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. 2003