疾病動物模式 - lac.nhri.org.tw

1 ( . ( . ). ) . Guide Guide for for the the Care Care and and Use Use of of Laboratory Laboratory Animals. Animals.. Public Public Health Health Service Service Policy Policy onon Humane Humane Care Care and and Use Use of of Laboratory Laboratory Animals Animals (PHS . (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, WF. outbred: Sprague-Dawley, Wistar, Long-Evans hamster Syrian hamster, Chinese hamster, European hamster ( ) ( ) ( ). gerbil Mongolian gerbil guinea pig inbred: Strain 2, Strain 13. outbred: Duncan-Hartley, Hartley rabbit New Zealand White Dutch dog Beagle, Grey hound Mixed breed(Mongrel). cat Domestic short hair Mixed breed nonhman-primate . ( ) . USA US Congress Office of Technology Assessment (1986). EU* Commission of the European Communities (1994). Japan Estimated on the side of caution Canada Canadian Council on Animal Care (1995) Resource 18.))

2 Switzerland Swiss Federal Office of Veterinary Care (1993). Report of the Australian Senate Select Committee on Australia Animal Welfare: Animal Experimentation (1989). others 10 Estimated on the side of caution Total ~ . 200 40000. 180 35000. Number of Animal Sales (thousand). 160. 30000. 140. Sales Amount in NTD. 25000. 120. 100 20000. 80. 15000. 60. 10000. 40. 5000. 20. 0 0. 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005. Number of Animal Sales 53 71 124 128 142 158 183 168. Sales Amount in NTD 1454 5209 7005 8836 1110 1608 1641 1859 2400 3350 3041. Number of Animal Sales Sales Amount in NTD. 91 92 93 . ( ) ( ).. *1 *2. 91 92 5 93 3 5 1900s .. 1920s .. 1930s .. 1940s .. 1950s .. 1960s .. 1970s .. 1980s .. 1990s , ..AIDS .. 30 . 30 25 . 25 . 10 . 10 20 . 20 . 15 . 15 .. 1. (Induced or experimental models) .. alloxane .. 2. (Spontaneous or natural models) .. 3. (Negative or non reactive models) .. 4. (Orphan models).

3 (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) . 2. 9.. 3. (1) . 4. (2) . 5. (3) . 6.. 10.. 7.. 8.. 11.. 1.. 2.. 3.. 4.. 1.. (1) (prospective) . (retrospective) . (2) .. (3) . 2.. 50 60 5 6 . 10 200 300 .. 4 5 . 5 20 .. 3.. 1.. (prototype).. 2.. 1. 2.. (1) . (1) . (2) (2) . (3) . (4) . (5) . (6) . (7) .. 9% .. 87%.. Rat Mice .. MICE. C57BL/6. BALB/c Rats SHR. Sprague-Dawley (hamster). (gerbil).. Beagle dog . 1. 9. (Myocardial ischemia) . 2.. models 10. (Cancer research) . 11.. (Transgenic and gene knock-out . animals). mellitus . 12. : . 6. (Viral hepatitis) (nuclear transfer) , 7. 13. (Animal (Atherosclerosis) models in toxicity testing). 8. (Cardiomyopathy) . 1.. (1) . (2) : Spontaneous hypertension rats (SHR).. polygenic .. WKY SHR/N. 2.. (1) . (cyclosporin) . (2) . (nu): T . (rnu): T.

4 C. Beige (bg): . d. X-linked immunodeficiency (xid) B . e. severe combined immunodeficiency (scid) . T B . f. non- obese diabetic (nod) : . T B NK macrophage .. SCID mice NOD-SCID. Nude mice . h. Osteopetrosis (op) .. i. Multiple mutant strains . scid-beige T B NK . nude-beige T NK . beige-nude-xid T B NK . nod-scid T B NK . i.. Chediak-Hagashi syndrome Defect in sorting pathway of secretory lysosome in immune cells and melanocytes Failure to fuse lysosome properly with phagosome Immunodeficiency (impaired intracellular killing). and albinism . models .. Antigen induced (in complete Freund's 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 mice K/BxN (KRN, NOD hybrid): antibody to GPI. MRL/l C57BL NZB.

5 (1)lpr (lymphoproliferation) . (2)ank (progressive ankylosis) . (3)moblo (mottled-blotchy) .. (1)ddy . (2)(NZB NZW)F1 . NZW/LacJ , NZB/B1NJ. mellitus . Hypoinsulinemia (juvenile-onset, insulin dependent, ketosis prone). (1)BB Wistar . (2) .. (3) . 1 3 . (4) Non-obese diabetic (NOD)mice autoimmune/Th1. (5) Streptozocin or alloxane-induced (6) C57BL/6-Ins2 Akita/J: congenic, insulin II gene( Ins2) .. Non-obese diabetic Chinese hamster . Hyperinsulinemia (maturity-onset, nonketotic, noninsulin-dependent, obesity). (1) . : KK mice C57BL/6J-Lepob/Lepob . : ZDF/Gmi-fa (Zucker diabetic fatty rat) . WDF/Ta-fa (Wistar diabetic fatty rat). Lepob/Lepob mutation 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 eating Ordinarily, high levels of body fat produce leptin, which inhibits eating.

6 Obese mice fail to produce leptin. Obese humans produce leptin but fail to respond to it.. Non-obese diabetic 129J-Leprdb/Leprdb C57BL/KsJ- Leprdb/Leprdb : C57 BLKS/J-m +/+ db (repulsion ) (intercross). m +/+ db x m +/+ db . m + /m + m + / + db + db/+ db 1 2 1. ( ) ( ). , ( ) , . 6. (Viral hepatitis). B . (Marmota monax): B . Woodchuck hepatitis virus (WHV): hepadnavirus Similarity between WHV and HHV. Chronic 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 = 50. Mice: high density = 50 low density > 100.

7 (mice is different from human, On the other hand, hamster is similar to human: high density is higher than low density cholesterol). 8. (Cardiomyopathy) . Dilated cardiomyopathy: TO-2 hamster Hypertrophic cardiomyopathy : 9. (Myocardial ischemia) .. C57BL/6- Xintm Hamster 10. (Cancer research) .. (Xenograft) . SCID .. E-B . (Burkitt's lymphoma). AKR . 11.. (Transgenic and gene knock-out animals). Cancer research - C57BL/6J-Trp53 tm1 Tyj (Trp:transformation related protein). - 129S1/SvImJ-Rb1 tm1 Tyj - H-Ras K-Ras transgene B6;SJL-Tg(WapHRAS)69 Lln Chr YSJL/J. Cystic fibrosis (cystic fibrosis transmembrane conductance regulator). Atherosclerosis C57BL/6J-Apoe tm1 Unc Diabetes NOD-Tg( ). Th1 Th2 double transgene (B6)-Cd4tm1 Knw/DvsJ (resistant). Anti-inflammation NOD-Tg (PGK-DcR3). (decoy receptor 3). 12. : . (nuclear transfer) , (Dolly sheep). (Wilmut et al., 1997).. (Investigational New Drug) .. (Investigational New Drug).

8 (New Drug Application).. ( ). 13.. (Animal models in toxicity testing). (1) . 24 .. (2) .. (discharge) . (3) .. ) . (4) . (GPM) .. (5) .. ICR mice SD .. Beagle Beagle dog dog .. (6) .. (7) .. 18-24 .. (8) .. Animal models for dental diseases Diseases Animal model Remarks Periodontal diseases Dog Porphyromonas gingivalis (periodontitis) Rats (F344). Hamster Cat Gingival overgrowth Rats (SD) Cyclosporin Dental caries Rats Streptococcus mutans (Mice) Streptococcus sobrinus Streptococcus gordonii Actinobacillus + sucrose + host cariogenic diet Osteoporosis Mice Biglycan (Bgn) deficient (Dental implantology) Rats mice Ovariectomized rats Calculus Rats High carbohydrate diet containing high amount of P, Ca, Mg Rats - Good animal model for dental diseases Information : anatomy, histology, flora, biochemistry of oral tissues etc. to every major oral diseases in humans 3. Adapt well to changes in environment, diet or husbandry 4.

9 Easy to manipulate: saliva & blood collection, administration of test agents, dietary manipulation 5. Costs are low Carious areas on the surface of mandibular molars Sectioned rat molars with carious lesions . ENU (E-ethyl-N-nitrosourea) . - . - . Laboratory Number Strain/Stock Laboratory Animal Animal Strains 1. SPF. BALB/cByJNarl BALB/cAnNNarl C57BL/6 JNarl CBA/CaJNarl Mouse 10 DBA/2 JNarl FVB/NJNarl C3H/HeNcrNarl Narl:ICR Narl:ICR-Foxn1nu BN/SsNNarl F344/NNarl LEW/SsNNarl Rat 8 SHR/NCrlNarl WKY/NCrlNarl, Narl:LE Narl:SD Narl:Wistar Hamster 1 Narl:Syrian hamster 2. Germ-Free C3H/HeNCrlNarl C57BL/6 JNarl Mice 4 BALB/cByJNarl Narl:Swiss Webster The New Strains to Breed Six stains in 2005: Prkdcscid/J The goal is to NOD/LtJ improve the quality and diversity of +/+ Leprdb/J. laboratory animal 129X1/SvJ stains including the rare strains. Two strains in 2006: KK/Ay BALB/cJ.. 2003.