17b. NHP Models

Marmosets (Callithrix jacchus) can be used to study?

-Parkinson's Dz - Induce w/ MPTP

-Aging & age related diseases

-Experimental allergic encephalomyelitis (EAE) = mimics multiple sclerosis

-Idiopathic hemochromatosis (iron accumulates in tissues)

-Aging and age related diseases

-Pharmacology, Toxicology, Neurophysiology (Lissencephaly), Reproductive biology, Viral oncology, Infectious and non infectious disease research

-Periodontitis

-Stroke research

-Yellow fever

-Hepatitis A

-Legionnaires Disease (L. pneumophilla)

-Lymphocytic thyroiditis (Hashimoto's dz)

-SARS Coronavirus

What is the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)?

-induce Parkinson's Dz

-selective degeneration of the substantia nigra after systemic administration

How is experimental allergic encephalomyelitis (EAE) induced in marmosets?

-MOG (myelin oligodendrocyte glycoprotein)

-MOG variant

The marmoset is the preferred model for what specific phase of multiple sclerosis?

relapsing/remitting

Zebra finches and _____ (NHP species) are both important species for studies of vocal communication

marmoset

Marmoset (Callitrhix jacchus)

What CITES level is Tamarins (Sanguinus oedipus)?

CITES I

What are Tamarins (Sanguinus spp.) in general used to study?

-stroke research

-yellow fever

The cotton topped tamarin (Sanguinus oedipus) is used to study what?

-chronic colitis

-colonic adenocarcinoma

-atherosclerosis

Colon cancer (S. oedipus)

Viral hepatitis (S. labiatus & S. mystax)

Cardiomyopathy (S. mystax)

The White lipped tamarin (Sanguinus labiatus) is used to study what?

-viral hepatitis

-crohn's dz

The mustached tamarin (Sanguinus mystax) is used to study what?

-viral hepatitis

-cardiomyopathy

-Crohn's disease

cotton topped tamarin (Sanguinus oedipus)

White lipped tamarin (Sanguinus labiatus)

mustached tamarin (Sanguinus mystax)

Owl Monkey (Aotus) can be used to study?

Malaria (P. falciparum and P. vivax)

Oncogenic virus model (herpesvirus)

Non-oncogenic virus (Hepatitis A)

Eastern Equine Encephalitis and Dengue research

Cutaneous and visceral leishmaniasis

Vision research

What characteristics of owl monkey makes them good for vision study?

nocturnal, lack tapetum lucidum, larger eyes with more spherical lens allowing for refraction and focus of an image on the retina at low light levels).

Their large retina has both rods and cones but decreased level of cones and more rods than other primates.

Red necked owl monkey (Aotus nancymaee)

Squirrel Monkey (Saimiri) can be used to study?

-CNS/Behavior/Learning/Perception

Natural glucocorticoid resistance

-Circulating levels of free / unbound cortisol is 100X greater than humans/ OWM

-Heart Failure and Cardiomyopathy

-Malaria

-transmissible spongiform encephalopathies

-Creutzfeldt Jakob Dz

-Pelvic organ prolapse (POP)

-yellow fever

-congenital hyperbilirubinemia

-lissencephaly

Why can squirrel monkeys be used to study Creutzfeldt Jakob's dz?

genetically susceptible to PrP gene (of CJ)

What squirrel monkey can be used to study congenital hyperbilirubinemia?

Bolivian (Saimiri boliviensis)

Bolivian squirrel monkey (Saimiri boliviensis)

Guanian squirrel monkey (Saimiri sciureus)

Rhesus (Macaca mulatta) can be used to study?

-AIDS research/HIV/SIV/SHIV

-Experimental Allergic Encephalomyelitis (EAE, to model MS, induce with MOG)

-Parkinson's via MPTP, Alzheimer's

-RBC Rh factor discovered

-Polio vax developed

-Aging

-Arthritis

-Atherosclerosis

-Drug safety/efficacy

-Endometriosis

-Immunodeficiency model

-Alcoholism

-Diabetes (obesity and diabetes, gestational diabetes, obesity and aging)

-Cancer

-Myocarditis

-Myopia

-Genetic research

-Tetanus

-Neonatal biliary atresia, congenital neonatal pneumonia, fetal pneumonia

-Meningioencephalocele

-Congenital hydrocephalus

-Venereal papilloma & squamous cell carcinoma & HPV

-Reproductive biology (Pre-eclampsia, Endometriosis, infection & pre-term labor, infertility)

-Osteoporosis

-Vesicoureteral reflux

-Drug addiction

-Infectious diseases (yellow fever, LCMV, leprosy, malaria [pregnancy and malaria], Lyme's disease , Epstein Barr virus, helicobacter pylori, Legionnaires Disease [L. pneumophilla], monkeypox, TB)

What is the most widely used model for parkinson's disease?

Macaca mulatta

Cynomolgus (Macaca fascicularis) can be used to study?

-Scrub typhus (model of choice)

-Reproductive biology (endometriosis)

-Oncology

-Periodontitis

-Trachoma

-ARDS

-Pharmaceutical research - standard macaque model

-Behavioral research

-Diabetes (therapies, gestational diabetes)

-Cardiovascular disease (atherosclerosis)

-Infectious diseases ( Cytomegalo virus, TB, measles, hepatitis A, AIDS research, LCMV, Hanta virus, monkeypox, Lassa fever)

-Retroviral studies

-Experimental Allergic Encephalomyelitis (EAE, to model MS, induce with MOG)

-Strabismus

-Subarachnoid hemorrhage

-Macular cyst

-Huntington's disease

-Osteoporosis

-Transmissible spongiform encephalopathies

How is strabismus induced in Macaca fascicularis (Cyno)?

botulinum A neurotoxin into extraocular muscles

How is a macular cyst induced in Macaca fasicularis (Cyno)?

perfluoropropane (C3F8) injection into eye

Pig Tailed Macaque (M. nemestrina) can be used to study?

-AIDS research/HIV/SIV

-Gene therapy

-Immunology studies

-Hearing

-Periodontitis

-Cryptosporidiosis

-Atherosclerosis

-Strabismus

-Parkinson's Disease via MPTP

-Diabetes

Stumptailed Macaque (M. arctoides) can be used to study?

-Baldness

-Behavioral studies

-Atherosclerosis

-Pulmonary hypertension (monocrotaline induced)

-AIDS research

-Myopia

Bonnet Macaque (M. radiata) can be used to study?

-Kyasanur Forest disease (Hard ticks borne viral haemorrhagic fever in South India)

-Reproduction biology

-nonalcoholic fatty liver dz

-diabetes

Macaca nigra (celebes or black crested macaque) can be used to study what?

-Type II DM (amyloid in islet cells)

Macaca fuscata (japanese macaque) can be used to study what?

-malaria

Rhesus macaque (Macaca mulatta)

Cynomologus / long tailed / Cyno / Crab eating Macaque (Macaca fascicularis)

Pig tailed macaque (Macaca nemestrina)

Stump tailed macaque (Macaca arctoides)

Bonnet Macaque (Macaca radiata)

Celebes, Black crested Macaque (Macaca nigra)

Japanese macaque (Macaca fuscata)

What NHP is the primary model for coronary heart and lung dz?

Papio anubis

What NHP is great for vaccine development because they have the same IgG subclasses (1,2,3,4) as humans?

Papio anubis

Baboons (Papio) can be used to study?

-Vax Development

-Heart and Lung Dz (atherosclerosis, hypertension)

-Infectious diseases - Whooping cough (Bordetella pertussis)

-Osteopenia

-Diabetes (obesity and diabetes, genetics of obesity, cardiovascular disease)

-Genetics, stem cell therapies

-Transplantation, biomedical device development

-Reproductive physiology (endometriosis, decreased ovarian function)

-Neonatal research

-Hepatitis C, Resp. syncytial virus (RSV)

-Strabismus

-Stroke research

-Spinal disorders

-AIDS research

-Adult T-cell leuk/lym (STLV-1) 🡪 Non Hodgkins Lymphoma

-Malaria (cerebral malaria)

-Huntington's Disease

-Drug addiction

Olive baboon (Papio anubis)

The silver leaf monkey (Presbytis cristatus) can be used to study?

-scrub typhus

-filariasis (Wuchereria bancrofti)

What causes scrub typhus?

Rickettsia tsutsugamushi

silver leaf monkey (Presbytis cristatus)

The indian leaf monkey (Presbytis entellus) can be used to study?

-scrub typhus

indian leaf monkey (Presbytis entellus)

The mantled guereza (Colobus guereza) can be used to study?

-Veneral papilloma and squamous cell carcinoma

-HPV

mantled guereza (Colobus guereza)

What NHP is the natural host of SIV?

What NHP is the reservoir for SIV?

Host - Mandrillus spp (mandrils) & Chlorocebus aethiops (african green)

Reservoir - Sooty mangabey (Cercoebus atys)

What can the gorilla be used to study?

Shigellosis

African Green (Chlorocebus aethiops) can be used to study?

-African trypanosomiasis

-Vaccine development

-AIDS research/HIV

-Leishmania

-Atherosclerosis/Metabolic Syndrome

-Hypertension

-Neurologic diseases (Parkinson's Disease via MPTP)

-Psychology/social behavior

-Diabetes (obesity and diabetes)

-Varicella (chickenpox)

-Leprosy

-Legionnaires Disease (L. pneumophilla

African Green (Chlorocebus aethiops) are a natural host of what dz?

SIV

Vero cells are a line from the kidney epithelial cells ow what NHP?

African Green (Chlorocebus aethiops)

African Green (Chlorocebus aethiops)

What can the Sooty mangabey (Carcocebus atys) be used to study?

-leprosy

-AIDS/HIV/SIV

Sooty mangabey (Carcocebus atys) are a natural host of what dz?

SIV

What can the Patas monkey (Erythrocebus patas) be used to study?

-infectious dz

-varicella

-pregnancy toxemia

Patas monkey (Erythrocebus patas)

What is an important difference in pregnancy toxemia in NHPs vs humans?

NHP version does NOT progress to eclampsia, coma, and death

What are the 4 natural hosts of SIV?

Mandrils, Chimps, Chlorocebus aethiops, and Cercocebus atys

Chimpanzees (Pan troglodytes) can be used to study?

-Hepatitis A and B Vx

-Hepatitis C = only animal model

-adenovirus

-RSV, Ebola, malaria and assoc. vax develop.

-Aerospace program

-Cognition and language

-Malaria

-Gonorrhea

-Neuroscience

-Immunology

-Behavioral studies

-AIDS research/HIV

-Leprosy

-Subarachnoid hemorrhage

Chimps area natural host of what dz?

SIV

Which NHP spp. can be used to study Cryptosporidiosis that resembles infection in young children?

Pigtail macaque (M. nemestrina)

Which NHP spp. is the best for Atherosclerosis model?

Macaques; Naturally occurring lesions Cyno>>>Rhesus.

Old World species are irreplaceable for investigating the influence of sex differences and sex hormones on the development of atherosclerosis and its sequelae*

What anatomy difference do squirrel monkeys, marmosets, tamarins have that make them a less than ideal model to study human atherosclerosis?

Lack the large epicardial coronary arteries (primary sites of development for human atherosclerosis)

African green monkeys (moderate) and baboons (high) have different prevalence of atherosclerosis, which one is prone to diet-induce atherosclerosis while the other one is resistant to diet-induce atherosclerosis?

African green monkeys prone to diet induce atherosclerosis but baboons are resistant

What is Monocrotaline (toxic pyrrolizidine alkaloid) used for?

Causes pulmonary hypertension

M. arctoides (stump tailed macaque)

What can be used to create strabismus in macaques?

resection of extraocular muscles or injection of Botulinum A

Myopia (Nearsightedness) can only be induced before ___ age?

Progressive axial elongation of the eye, is often accompanied by fundus changes, and can only be induced before eye growth has been completed

NHPs for diabetes model

Cynos: DM drug therapies, gestational diabetes

Rhesus: relationship btwn obesity and diabetes, gestational diabetes

AGM: relationship btwn obesity and diabetes; unique b/c trait diabetic parameters are inheritable

Baboons: more recent model of obesity and diabetes, used to study genetics of obesity

NHP: Papio Anubis is a popular species for xenotransplant, what are the three characteristics make them great model for xenotransplant?

Nonendangered, readily pro-creates, mimic human response

Baboons, like the human, have histo-blood groups A,B, and O

Erythrocebus patas (Patas monkeys) & Chlorocebus aethiops are great model for ______ because disease resembles clinical signs in children except for its unusual severity

Varicella (AKA chickenpox)

Patas dz = 50% or greater case fatality rate

Cercocebus torquatus atys (sooty mangabey), Pan troglodytes, Chlorocebus aethiops, M. mulatta are suitable to study this disease that also occurs in Armadillo spreading to human

Leprosy (Mycobacterium leprae)

How is yellow fever transmitted?

Flavivirus - transmitted by Aedes mosquitoes

Yellow fever = viral hemorrhagic disease

Which NHP spp was used to develop vaccine for yellow fever?

Macaca mulatta (rhesus macaques)

Yellow fever one of the earliest reasons for regulating the importation of NHP's

Which NHP spp was used to study Lyme Neuroborreliosis (Borellia burgdorferi)?

Rhesus (model of choice)

Rhesus demonstrate clinical and pathological features of the dz: rash (erythema migrans), myocarditis, CNS meningitis, polyarthritis

NHPs only model to consistently produce CNS signs infected people develop

How is Lyme Neuroborreliosis (Borellia burgdorferi) transmitted?

tick

Which NHP spp was used to study Leishmania?

Chlorocebus aethiops, Macaca Mulatta

Owl monkeys have also served as a model for cutaneous and visceral leishmaniasis

A more recent study suggests that owl monkeys have developed resistance against Leishmania infantum chagasi

Which NHP spp is more susceptible to Tuberculosis?

Cynos

Rhesus

Rhesus

both rhesus and cynos for vaccine testing, immunology, drugs and pathogenesis

What strain of mycobacterium is used for make vaccine for TB, "Bacillus Calmette Guerin"?

Attenuated form of M. bovis, does not prevent infection, usually ↓ severity of dz

Rhesus, Cotton-top tamarin can be used to study which herpes virus that associates with Infectious Mononucleosis, Hodgkin Lymphoma, Nasopharyngeal Carcinoma, and lymphomas in immunosuppressed human?

Epstein-Barr Virus (human herpes virus 4)

Which NHP species can be used to study Male Pattern Baldness in human?

Stump tailed macaque (M. arctoides)

~4yrs 🡺 increased testosterone 🡺 signs of male-pattern baldness along frontal scalp

Which NHP species was used extensively in Hepatitis A/B/C research?

chimpanzee.

Owl monkey: excellent model for Hepatitis A

What is the purpose of fMRI?

functional magnetic resonance imaging can be used to noninvasively assess pain and to confirm analgesic efficacy of currently used products.

Yellow parts = brain activated by noxious stimuli

What disease can be induced if expose to (MPTP) 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine acutely?

Parkinson's Disease

Clinical signs a result of loss of dopaminergic neurons in the substantia nigra pars compacta and reduction of neuronal processes extending to the striatum. Intracytoplasmic neuronal inclusion (lewy bodies) can be present.

What is the underlying cause of Alzheimer's Disease? deposition of ? in the brain

Progressive cerebral deposition of the amyloid beta‑protein (ABP)

What disease can be induced with Myelin oligodendrocyte glycoprotein (MOG)? What disease model?

fatal encephalomyelitis

Experimental Allergic Encephalomyelitis (EAE) = Model for Multiple Sclerosis

Rat- Lewis (myelin basic protein and CFA) and Dark Agouti (myelin basic protein and IFA)

What methods can be used to induce Huntington's Disease in Cyno (M. fascicularis), Baboon (Papio sp)?

1. Transgenic Rhesus model w/HTT (huntington gene) via lentiviral delivery

2. injections with glutamate or excitatory amino acids (guinolinic acid, kuinic acid, or ibotenic acid)

-- 3-nitropropionic acid (3-NP model, inhibitor of the mitochondrial citric acid cycle)

HD is a progressive neurodegenerative disease with autosomal dominant inheritance

What compound can be used to create Huntington's Disease in rat?

Quinolinic acid (QA) lesion

Which hormone causes endometriosis in macaques/ baboons?

estrogen

What are the pathology lesions associated with endometriosis?

Firm white nodules with cyst like structures filled with red/brown fluid (chocolate cysts = pathognomonic)

What methods can be used to create Osteoporosis in NHPs?

Ovariectomized consistently develop osteopenia with high bone turn over rate

Which NHP species is good model for reproductive tract disorders?

Baboons

Which animal species is the best model for Legionnaires' Disease?

Guinea Pigs (Cavia procellus)

How to create Legionnaires' Disease in NHPs?

aerosolized Legionella pneumophila

Causes acute fibrinopurulent bronchopneumonia; severity of disease is dose dependent

How to induce asthma model in Cynos macaque?

Natural infection with Ascaris suum 🡺 allergic reaction similar to human atopic asthma

What are the two forms of degenerative arthritis?

1.Osteoarthritis

2.Calcium pyrophosphate dehydrate crystal deposition dz

How to induce Spongiform Encephalopathy (e.g. CJD) in NHPs?

Oral or IV transmission

Lemurs fed BSE-infected cattle brain developed CJD-like disease