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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

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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