JAX® In Vivo Services Drug Efficacy Studies: Diabetes Example

JAX® NOTES Issue 505, Spring 2007

JAX® In Vivo Services at JAX® West, Sacramento, California, can perform a variety of drug efficacy studies for biomedical researchers. The studies are performed in our state-of-the-art facilities, use a series of high-throughput and non-invasive phenotyping platforms, are highly customizable, and can be performed either with investigator-supplied mice or with JAX® Mice purchased directly from The Jackson Laboratory. The sample efficacy study presented below is designed to characterize either three type 2 diabetes therapies or one therapy at three dose levels. (The next several issues of JAX® NOTES will present similar hypothetical drug efficacy studies for obesity, inflammatory bowel disease, and atherosclerosis.)

JAX® In Vivo Services performs flexible and customizable studies. This sample study provides an example of a protocol designed to characterize three diabetes therapies or one therapy at three dose levels.

Study Design:

Mice from the diabetes model of your choice, along with 10 wild-type controls, will be transferred to The Jackson Laboratory In Vivo Services and allowed to acclimate for one week. They will be housed 5 per cage with ad libitum access to standard chow and water. The study will proceed with four weeks of daily dosing and a terminal necropsy procedure.

Dosing Protocol:

PO, once daily for 28 days

Group  Strain n =    Treatment
1 Wild-type Control   10 Naive
2 Diabetes Model 10 Vehicle Control
3 Diabetes Model 10 Rosiglitazone
4 Diabetes Model 10 Test article 1
5 Diabetes Model 10 Test article 2
6 Diabetes Model 10 Test article 3

 

Procedures and Timeline:

Clinical observation and body weight are performed weekly. Fed glucose is measured by glucometer twice weekly. Fasted overnight glucose tolerance, with RO blood collection for enzymatic glucose, is performed prior to dosing (Day 0) and at Days 14 and 28. Necropsy with blood and tissue collection is performed on Day 29.

Cost Estimate:

Item Description Cost

60 Mice Total

 50 Diabetes Model Mice + 10 Wild Type Mice Varies

Housing

 5 Weeks of Housing at 5 mice per cage $

950

Procedures

 GTT (IP, IV or Oral), FG, Daily Gavage, Tissue Harvest, glucose measurement, insulin measurement $

34,900

Project Management

 Administration, Protocol Customization, Facilities, Equipment, Quality Assurance, Health Monitoring, Supervisory Staff, Data Review, Client Communications and Final Report $

4,750

Total Total Costs Not Including Mice $

40,600

 

 

 

 

Representative Results:

Fasted oral glucose tolerance tests (GTT) assess blood glucose levels by glucometer at t=0, 15, 30, 60 and 120 minutes post glucose delivery (n=10). The baseline measurement (t=0) also represents a fasted glucose when analyzed independently.

 

Following 0, 14 or 28 days of Rosiglitazone treatment dose (25 mg/kg), db/db (BKS.Cg-m +/+ Leprdb/J) mice have a time-dependent decrease in both fasted glucose and GTT area under the curve (AUC) as compared to vehicle treated controls.

Other Procedures to Consider for Your Study:

 

Dosing Dosing can be performed QD, BID, IP, IV, SC, PO, high pressure tail vein, osmotic minipumps (SC or IP), SC drug pellets, in the food or water
Glucosuria Twice-weekly glucosuria: a positive glucosuria test followed immediately by blood glucose by glucometer and positive glucometer repeated 2 to 3 days later (marks onset of diabetes)
Food or Water Intake Weekly food or water intake measurements per cage
Comprehensive Cage Monitoring System Individual food & water intake, O2 & CO2 exchange, and activity
Activity Locomotor activity
Echo MRI Scan Body composition analysis (fat, lean or bone content) on each mouse
Terminal Blood Chemistry Panel Serum chemistry, lipid distribution, and multiplex analysis of serum hormones and cytokines (insulin, leptin, adiponectin, TNF-a, IL-6, resistin, MCP-1, PAI-1, HbA1c, etc.)
Histology and Slides Slide preparation with interpretation

 
 
Sample Report:

All data is thoroughly recorded in the spirit of GLP and is provided to you in electronic format. A final report will be submitted to you, if requested, detailing the approved study protocol, protocol deviations, reportable data and optional data analysis.

The Jackson Laboratory offers the most widely used mouse models for type 2 diabetes, including emerging models such as the NONcNZO10/LtJ (004456). Many of these are described in detail in our Type 2 Diabetes and Obesity Resource Manual, available free by filling out the literature request form.

If you would like JAX® In Vivo Service to perform a drug efficacy study for you, please visit the JAX® Services Web site, send an e-mail to jaxservices@jax.org, or call JAX® Services at 1-800-422-MICE (6423) or 1-207-288-5845.