PD/Efficacy Models

In vivo metabolic profile

• Glucose tolerance tests (PO/IP/IV)
• Insulin tolerance test
• Mixed meal tolerance test
• Oral lipid tolerance test
• VLDL secretion rates
• Insulin/glucose clamps (hyperglycemic/euglycemic-hyperinsulinemic)
• Substrate partitioning: assessment of glycogen synthesis and lipid synthesis post glucose load
• Energy expenditure assessment (Indirect calorimetry)
• Biomarker assessment to support proof of activity/mechanism (multi-analyte detection)

In vivo cardiovalscular profile

• Rat and mouse telemetry for blood pressure (BP) and ECG measurement
• Invasive BP measurement via carotid/femoral artery in conscious and freely moving rats
• Non-invasive BP measurement using tail cuff method

Animal Models for Efficacy Assessment

• Diet induced obese (DIO) mice fed with diet containing 60% or 45% Kcal from fat source,
• High cholesterol fed hamsters model of atherosclerosis
• Spontaneous mutations
  • db/db mice and ob/ob mice
  • Zucker fatty rats and Zucker diabetic fatty rats
  • Spontaneously hypertensive rats (SHR)
• Chemically induced
  • STZ-induced type 1 diabetic rats
  • neonatal STZ diabetic rats
  • STZ + DIO mice
  • Mild-STZ-induced Type 1 diabetic mice
• Surgical
  • Uninephrectomized rats/mice
  • Uninephrectomy + DOCA treated rats

Ex vivo assays

• Isolated “Working” heart to study cardiac function and metabolism
• Isolated perfused heart (Langendorff mode) forcardiac function
• Receptor pharmacology using isolated tissues, e.g. aortic/fundus strips

Acute inflammation:

• Carrageenan induced rat paw edema
• LPS induced endotoxemia
• Air-pouch model
• Arachidonic acid induced ear edema

Respiratory inflammation:

• Bleomycin induced pulmonary fibrosis in C57BL/6J mice
• Ovalbumin (OVA) and ragweed induced allergic asthma in BALB/c mice
• LPS induced acute lung inflammation in Wistar rats

Inflammatory bowel diseases:

• DSS induced ulcerative colitis model in mice
• TNBS (Trinitrobenzenesulfonic acid) induced Crohn’s disease model in rats

Joint inflammation:

• Collagen Type-II induced arthritis (CIA) in mice
• Adjuvant induced arthritis (AIA)
• Collagen antibody induced arthritis (CAIA)

Skin inflammation:

• Imiquimod-induced psoriasis in BALB/c mice

Systemic Lupus Erythematosus

• MRL/lpr mouse model of SLE
• NZBWF1/J mouse model of SLE

Multiple Sclerosis

• MOG_35-55-induced EAE in C57BL/6 mice

Liver Fibrosis/NASH

• CCl4-induced rat model of liver fibrosis
• MCD diet induced liver fibrosis in mice

Kidney fibrosis

• Unilateral Ureteral Obstruction (UUO) model in mice
• Folic acid induced kidney fibrosis in mice

The models are supported by strong expertise in ex vivo assays, histopathology, and PD marker studies

Hemorrhoid Model In Rat

• Croton Oil-Induced Hemorrhoid Model In Rat

Anti- Parkinson’s: Primary & Secondary Models

• Haloperidol induced catalepsy in rat model
• 6-OHDA induced circling behavior in nigrostriatal lesioned rats (acute and chronic )
• Levodopa- induced dyskinesia and rotational behavior in hemiparkinsonian rats (acute and chronic)
• Tremorine and Oxtremorine antagonism/induced tremors/ataxia/spasticity/ salivation/lacrimation/hypothermia

Anti-Depressants:

• Tail suspension in mice
• Despair swim test in rats/mice
• Apo-morphine-induced hypothermia in mice
• Novelty Suppressed Feeding (NSF) Test in rat and mice

Cognition:

• Object recognition test

Cerebral ischemia (MCAO)

• Middle Cerebral Artery Occlusion rat model

Behavior and Motor Coordination

• Rotarod Method
• Locomotor activity in open field test
• Morris water Maze
• Y/T Maze Test

Safety Pharmacology Core Battery

• Irwin’s Battery test in mice and rat

Anti-Epileptic Activity

• Pentylenetetrazole induced Convulsions

Blood-brain barrier (BBB) integrity

• Acute effect of LPS using Evans blue

Anti-Anxiety activity

• Staircase test
• Elevated Maze
• Resident-Intruder/Isolation Aggression test

Acute Pain models

• Acetic acid induced writhing
• Hot plate model (central) in mice and rat
• Post surgery acute pain
• LPS-induced inflammatory pain
• Mild Thermal Injury Model
• Carrageenan/Capsaicin induced thermal/mechanical hyperalgesia
• Tail flick/Tail immersion test or other radiant heat methods

Chronic: Neuropathic pain model

• Spinal nerve ligation (SNL) model of neuropathic pain
• Sciatic nerve ligation (Partial) in rat model
• CFA induced model of inflammatory pain
• Chemotherapy (Cisplatin)-induced peripheral neuropathic pain rat model
• Formalin-induced pain (persistent pain model)
• Buprenorphine-induced tolerance/withdrawal in Cispaltin-induced neuropathic pain model
• Mono-iodoacetate induced osteoarthritis

Syngeneic animal models

• Lung cancer model in C57BL/6J mice
• Breast cancer model in BALB/c mice
• CT-26 Syngeneic Colon Cancer Mouse Model

Xenograft models

• Eurofins Advinus offers heterotopic (subcutaneous) xenograft models in immuno-deficient mice using
  • Cell lines provided by the client
  • > 20 cell lines available with Eurofins Advinus
  • Procured from ATCC on behalf of the client
• Following are the immuno-deficient mice available for xenograft
  • BALB/c Nude or B6 Nude (T cell deficient
  • NOD Scid (T and B cell deficient)
  • NOG or NSG mice (T, B and NK cell deficient)

Models under Development

Chemical-induced cancer model

• Azoxymethane+DSS-induced Colorectal cancer model in BALB/c mice

Fibrosis models

A range of animal models of Fibrosis are on offer for screening anti-fibrotic activity:

• Lung Fibrosis:
  • Bleomycin-induced lung fibrosis
• Liver Fibrosis:
  • Carbon tetrachloride (CCl4)-induced liver fibrosis in rats
  • Methionine choline-deficient (MCD) diet-induced mouse model of nonalcoholic steatohepatitis (NASH)
• Kidney Fibrosis
  • Unilateral ureteral obstruction (UUO)-induced kidney fibrosis
  • Folic acid-induced kidney injury and early fibrosis
• All the models are supported by
  • Detailed histopathology analysis
  • Gene expression analysis by qPCR
  • Immuno-histochemistry
  • Cytokine estimations
  • PK-PD correlations including tissue compound concentration

Gastro-intestinal Diseases

• Gastric Ulcers
  • Indomethacin induced ulcer model
    • Ethanol induced ulcer model in rats
    • Pylorus Ligation Induced Ulcer Model in rats
    • Cold Restraint stress Induced Ulcer (CRU) Model in rats
• Gastric Motility
  • Gastric emptying time (Charcoal based)

Urology

• Rodent cystometry

Ophthalmology

• STZ-induced diabetic retinopathy in rats; wherein:
  • Biochemical parameters, mRNA expressions for biomarkers, histopathology