P.I.: Richard Paylor, Ph.D.

Location:

Department of Molecular and Human Genetics
Baylor College of Medicine
Houston TX 77030

Description: Our laboratory has extensive experience examining a wide range of behavioral phenotypes in knockout and transgenic mice as well as various inbred strains. Our behavioral test battery assays multiple domains of CNS function. Our typical battery includes the following evaluations/assays:

• a simple neurological screen for basic sensory/motor function,
• open-field test for exploratory activity and anxiety-related traits,
• light-dark exploration box for anxiety-related traits,
• an accelerating rotarod test for motor coordination and skill learning,
• prepulse inhibition for sensorimotor gating,
• acoustic startle habituation for sensorimotor adaptation,
• contextual and auditory conditioned freezing for conditioned fear learning,
• Morris water task for spatial learning and memory, and
• the hot-plate test for analgesia-related responses.

Positive phenotypes can then be explored further using other assays in the lab. We have utilized this type of battery to evaluate a number of knockout and transgenic mice (see references listed below). We are currently developing a modified test battery for high-throughput evaluations which will include the neurological screen, open-field, light-dark test, rotarod test, prepulse inhibition test, and conditioned fear test. The development of each of these responses is also under investigation using different inbred strains of mice.

Screening Protocol:

For our behavioral analysis of mutant (knockout or transgenic) and wild-type mice we typically receive our mice at least 10 days before we start testing. Although our goal is to test approximately 15-20 mice of each genotype (approximately equal number of both genders) we prefer to test them in 2-4 small batches of mice. All testing is performed by a trained experimenter that is blind to the genotype of the mice. Each batch of mice must contain mutant and wild-type mice. Each batch of mice is then run through our entire test battery (listed above). We allow one week between most tests, however, we increase this to 2-4 weeks between the learning and memory tasks. Once all batches of mice have been completed we break the genotype code and analyze the data using appropriate statistical analyses. If a positive phenotype is obtained, then we replicate this finding in a entirely new batch of mice. Alternatively, we will run a second replicate set of mice through the entire test battery. This protocol is used to help ensure that any positive phenotype is reliable and sufficiently robust that it can transcend the environmental differences that normally occur when testing occurs over many days. Currently, we are developing a rapid test battery (listed above) that will assess several different CNS functions using a two week test protocol. Our goal is to assess the behavioral responses of 100-200 mice every two weeks.

Contact: If interested, please email Richard Paylor, Ph.D. with a brief description of the project.

Selected References:

1.Wehner, J.M., Bowers, B.J., and Paylor, R. (1996). The use of null mutant mice to study complex learning and memory processes. Behavior Genetics, 26, 301-312.

2. Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., Shiloh, Y., Crawley, J.N., Ried, T., Tagle, and Wynshaw-Boris, A. (1996). Atm-deficient mice: a paradigm of ataxia-telangiectasia. Cell, 86, 159-171.

3. Crawley, J.N. and Paylor, R. (1997). A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Hormones and Behavior, 31, 197-211.

4. Paylor, R., and Crawley, J.N. (1997). Inbred mouse strain differences in the prepulse inhibition model of schizophrenia. Psychopharmacology, 132, 169-180.

5. Crawley, J.N., Belknap, J.K., Collins, A., Crabbe, J.C., Frankel, W., Henderson, N., Hitzemann, R.J., Maxson, S.C., Miner, L.L., Silva, A.J., Wehner, J.M., Wynshaw-Boris, A., and Paylor, R. (1997). Behavioral phenotypes of inbred mouse strains. Psychopharmacology, 132, 107-124.

6. Lijam, N., Paylor, R., McDonald, M.P., Crawley, J.N., Deng, C.-X., Herrup, K., Stevens, K.E., Maccaferri, G., McBain, C.J., Sussman, D.J., and Wynshaw-Boris, A. (1997). Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell, 90, 895-905.

7. Sterneck, E., Paylor, R., Jackson-Lewis, V., Libbey, M., Przedborski, S., Tessarollo, L., Crawley, J.N. and Johnson, P.F. (1998). Mice lacking the traanscriptional regulator C/EBP display specifically enhanced contextual fear conditioning. Proceedings of the National Academy of Science, 95, 10908-10913.

8. Paylor, R., Nguyen, M., Crawley, J.N., Patrick, J., Beaudet, A., and Orr-Urtreger, A. (1998). 7 nicotinic receptors are not necessary for hippocampal-dependent learning or sensorimotor gating: A behavioral characterization of Acra7-deficient mice. Learning & Memory, 5, 302-316

9. Paylor, R., Hirotsune, S., Gambello, M.J., Yuva-Paylor, L., Crawley, J.N., and Wynshaw-Boris, A. (1999). Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice. Learning & Memory, 6, 521-537.

10. Kimber, W., Patrick, H., Hirotsune, S., Yuva-Paylor, L., Sutherland, H.S., Chen, A., Ruiz-Lozano, R., Liyanage, M., Hoogstraten-Miller, S., Chien, K., Paylor, R., Scambler, P.J., and Wynshaw-Boris, A. (1999). Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse. Human Molecular Genetics, 8, 2229-2237.

11. Prakash, S.K., Paylor, R., Lamarche-Vane, N., Armstrong, D.L., Xu, B., Mancini, M.A., and Zoghbi, H.Y. (2000). Functional analysis of ARHGAP6, a novel GTPase-activating protein for RhoA. Human Molecular Genetics, 9, 477-488.

12. Peier, A.M., McIlwain, K.L., Kenneson, A., Warren, S.T., Paylor, R., and Nelson, D.L. (2000). (Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features. Human Molecular Genetics.