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MAJ Eric Lombardini, VMD, DACVP, DACVPM
Armed Forces Radiobiology Research Institute
Uniformed Services University of the Health Sciences
Sus scrofa domestica
Miniature Pigs Miniature variants:
Yucatan miniature Ossabaw Banna Ohmini Pitman-Moore Chinese Dwarf Meishan Vietnamese
Micro variants: Göttingen Hanford Sinclair S-1 (Hormel) NIH
Physiology/Anatomy Weight: 12-45 kg at sexual maturity
Uterus is bicornate
Gestation is +/- 114 days in domestic swine (a few days less in miniatures)
Sexual maturity ranges from 4-6 months
Pig Glossary: Shoat: Weaned animal
Gilt: Immature female
Sow: Sexually mature female
Barrow: Castrated male
Boar: Sexually mature male
Suitability as a model Transgenic animals Short gestation time Conscious stress free animals Manageable/easy to transport Similarities between pig and human:
Pharmacokinetics after SC administration of drugs GI morphology and function Integumentarysimilarities Metabolic physiology Large volumes of blood can be obtained Catheter-implantation Risk of infection
Minipig models of human disease Reproductive toxicology Xenotransplantation Orthopedic surgery Dermal toxicity Heart disease Osteoperosis Radiation Teratogenicity Caisson disease Diabetes Parkinson Etc….
Eric Lombardini
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Reproductive toxicity Pyrimethamine
N-alkynitrosureas
http://minipigs.dk/fileadmin/filer/Publications/Malformations_in_the_Goettingen_Minipig.pdf
Allograft and burn research
J Burn Care Res. 2008 Nov-Dec;29(6):907-16. Review
Oronasal fistula repair
British Journal of Oral and Maxillofacial Surgery 48 (2010) 131–135
Phototoxicity Radiation research
Eric Lombardini
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Husbandry issues
Salt toxicosis
Microcytic/hypochromic anemia
Cannibalism
Disease prevention (Vaccinations): Erysipelotrix
Pasturella
Bordatella
Escherichia
Clostridium
Parvovirus
Rotavirus
Congential abnormalities
Dental malformation Claw overgrowth
Background pathology Testicular hypoplasia
Epididymis: Cysts and sperm granulomas
Skeletal mucle: Pale foci
Hemorrhagic syndrome (Thrombocytopenic purpura)
Serous atrophy of bone marrow adipose
Fibrinoid arteritis
Lungs: Focal mineralization
Alveolar histiocytosis
Mononuclear infiltrates
Eric Lombardini
Melanosis Pigmentation in internal organs – Normal in pigmented swine
Meninges, lungs, spleen, heart valves, liver, lymph nodes
Cornell Veterinary Medicine
5/11/2011
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Systemic pathology Integument Similarities and differences with humans:
Eric Lombardini
Thrombocytopenic Purpura Syndrome Gottingen piglets
Immune-mediated thrombocytopenia (platelets
<20,000/ul) and anemia
Disseminated visceral hemorrhages
Cutaneous purpura
Eric Lombardini
Porcine Juvenile Pustular PsoriaformDermatitis (Pityriasis rosea)
Cornell Veterinary Medicine
Melanoma
Cornell Veterinary Medicine
Papillomas
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Miscellaneous Other cutaneous pig diseases are seen rarely if ever
in laboratory minipigs
Staph hyicus (greasy pig disease)
Erysipelothrix rhusiopathiae (diamond skin disease)
Parakeratosis (zinc-responsive dermatosis)
Ringworm
Dermatosis vegetans
Musculoskeletal
http://pptox.dk/portals/0/12_poster.pdf
Necrotizing myositis
Brian Caserto
Eric Lombardini
Respiratory
Minipigs are genetically susceptible to all porcine
respiratory diseases
Actual disease rare in the lab setting:
SPF / barrier-raised pigs
Vaccination
Husbandry
Should always perform complete necropsy on acute
pigs to protect herd health
Porcine Respiratory Disease Complex Primary pathogens
M. hyopneumoniae
A. pleuropneumoniae
SIV
PRRSV
PRV
PRCV
PCV
Secondary pathogens
P. multocida
S. suis
H. parasuis
B. bronchiseptica
A. pyogenes
**A. pleuropneumoniae
Cornell University
PCV-2
http://www.pig333.com/circovirosis
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Mononuclear interstitial pneumoniaBordatella and Pasturella
Cardiovascular
Cardiovascular physiology, especially stress-related responses
Similar heart and great vessels
Coronary arterial blood supply
No collateral vessels in myocardium
Coronary artery can be clamped to induce myocardial infarct
Postprandial lipemia
Similarities to humans:
Eric Lombardini
Atherosclerosis
University of Pennsylvania
Study by Christoffersen et al (2007) showed females Göttingen Minipigs to be more obese, more insulin resistant and had a more atherogenicprofile than males
Arteritis Göttingen minipigs
Degenerative vascular lesions in small- to
medium-sized muscular arteries
Coronary arteries and vessels of the renal
pelvis are most consistently involved
Ventricular Septal Defect (VSD) Specific Yucatan mini- and micropig lines are models
for VSD
Occurs in about 20% of fetuses
65% are high membranous defects
Polygenic defect
Cornell University
5/11/2011
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Omnivorous
Large stomach, long small & large intestine
Gastric cell types and secretions
Digestion, absorption, pH changes
Small intestinal transit time
Tooth development
Similarities to humans:
Digestive
http://www.skullsite.co.uk/Pig/pigdom.htm
Begins with hyperkeratosis of the esophagus
and/or pars esophagea
Related to anorexia or finely ground, pelleted
feed – decreased gastric emptying
Stomach acid damages the
squamous epithelium
Exacerbated by stress
Gastric Ulcer Syndrome
J. Pohlenz
PCV-2
Eric Lombardini
http://www.thepigsite.com
Urinary
http://www.pig333.com/circovirosis
Göttingen and Sinclair S-1
Interstitial mononuclear cell infiltrates
Tubular degeneration and loss
Tubular ectasia and proteinosis
Basement membrane thickening
Glomerulosclerosis
Fibrosis
Interstitial nephritis CNS development; brain growth spurt before
birth
Majority of CNS cell division before birth
Myelination largely postnatal
Blood-brain barrier relatively immature at birth
Highly developed eye
Ideal for teratology studies
Similarities to humans
Nervous/Special Senses
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Salt intoxication
Eric Lombardini
Göttingen minipigs
Folds or “rosettes” in retina
Congenital background lesion
Retinal dysplasia
Eric Lombardini
Resources• Svenson, The Minipig in Toxicology
• Bollen et al, The Laboratory Swine
• Swindle, Swine in the Laboratory
• Gad, Animal Models in Toxicology
• Hau & Van Hoosier, Handbook of
Laboratory Animal Science, Vol. 3