JAX®  In Vivo Services Drug Efficacy Studies: Sample Morris Water Maze Study

JAX® NOTES Issue 506, Summer 2007

JAX® In Vivo Services in West Sacramento, Calif., can characterize the phenotypes of disease models or perform a variety of drug efficacy studies for biomedical researchers. These services are performed in state-of-the-art facilities using 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 us. The sample study below describes the use of the Morris Water Maze to characterize learning or memory impairment. (This is the second in a series of JAX® NOTES articles featuring sample studies performed by JAX® In Vivo Services.)

The Morris Water Maze is used to test hippocampus-dependent learning, including acquisition of spatial memory, long-term memory, and long-term spatial memory. It is also used to test general learning (non-spatial). Research areas involving learning or memory function include the following:

  • Alzheimer's Disease
  • Stress
  • Traumatic Head Injury & Stroke
  • Seizure Disorders
  • Aging & Dementia
  • Women's Health
  • Developmental Disorders
  • Sleep Disorders
    		•

    Sample Study Design:

    For phenotyping, 6 male and 6 female test mice, plus matching wild-type (WT) controls, will be transferred to The Jackson Laboratory In Vivo Services and allowed to acclimate for one week. They will be housed 3 per cage with ad libitum access to standard chow and water.

    • Morris Water Maze acquisition of spatial memory test (5 to 15 days of testing with up to 5 tests per day, each test consisting of 2 runs)
    • A run begins with mouse placed in pool of opaque water containing a hidden rescue platform and ends when the mouse climbs onto the platform
    • Outcomes & Analysis
      1. Latency to platform (max = 60 seconds)
      2. Swim distance
      3. Average swim speed
      4. Exploration pattern
    Procedures & Timeline:

    Acquisition of Spatial Memory Test

    Day

    -7 to 0

    1

    2

    3

    4

    5

    Activity

    Acclimation

    1-5 tests, 2 runs each

     

     

     

    Representative Results:

    Genetic Model of Cognitive Deficit: Scrambler (STOCK A/A-Dab1scm/J, 002043)

    Scrambler mice have a mutation in the Dab1 gene, resulting in, among other brain abnormalities, a major disorganization of the hippocampus. As can be seen from the data below, the Morris Water Maze testing allows for the discrimination of wild-type (WT) and mutant mice based on memory acquisition and retention.

     

    Global Tests of Water Maze Phenotyping (Scrambles vs. WT)
    (Error Bars = SEM, Paired T-test p < 0.0001)

    Acquisition of Spatial Memory: Testing of Scrambler or wild-type female mice for acquisition of spatial memory over 15 days.

    Probe Global Testing of Scramblers
    (MANOVA of Time by Group Interaction p = 0.09, Error Bars = SEM)

    Testing of Memory: Spatial Probe Trial of Scrambler or wild-type female mice for retention of memory at 6 and 12 days post-training.

    Other Procedures to Consider for Your Study:

    Dosing:

    Dosing can be performed IP, IV, SC, PO, high pressure tail vein, osmotic minipumps (SC or IP), SC drug pellets, in the food or wate

    Spatial Probe Trial:

    This optional protocol is performed the day after the acquisition phase for up to 5 runs for the test. The mouse is placed in the same pool of water with the platform removed, and the percentage of time spent in each quadrant of the pool is analyzed.

    Reversal Test for Working Memory:

    This optional protocol is performed the day after the acquisition phase for up to 5 runs for the test. The mouse is placed in the same pool of water with the platform moved to the opposite quadrant. The latency to the platform in the new location and exploration patterns are analyzed.

    Motor Function / Activity:

    Locomotor activity assessed to rule out confounding motor impairment

    Terminal Blood Chemistry:

    For pharmacokinetic

    Histology and Slides:

    Slide preparation with interpretation for phenotyping