Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models
| Autor: | Mayte Suárez-Fariñas, Liliana B. Menalled, Christina Leahy, Larry Park, Allan J. Tobin, Ethan Signer, Vanessa C. Wheeler, Monica Patry, Daniela Brunner, Marcy E. MacDonald, Janet M. Leeds, A. Jennifer Morton, X. William Yang, David Howland, Bassem F. El-Khodor, GP Bates, Benjamin Zahasky, Samantha J. Orenstein |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Aging Genotype Mice Transgenic Nerve Tissue Proteins Disease Motor Activity Neuropsychological Tests Article lcsh:RC321-571 Mice Huntington's disease medicine Huntingtin Protein Animals Humans Gene Knock-In Techniques lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Prepulse inhibition Sex Characteristics Environmental enrichment Behavior Animal Nuclear Proteins medicine.disease Phenotype Disease Models Animal Huntington Disease Neurology Female Trinucleotide repeat expansion Hypoactivity Psychology Neuroscience |
| Zdroj: | Neurobiology of Disease, Vol 35, Iss 3, Pp 319-336 (2009) |
| ISSN: | 0969-9961 |
| Popis: | Huntington's disease (HD) is one of the few neurodegenerative diseases with a known genetic cause, knowledge that has enabled the creation of animal models using genetic manipulations that aim to recapitulate HD pathology. The study of behavioral and neuropathological phenotypes of these HD models, however, has been plagued by inconsistent results across laboratories stemming from the lack of standardized husbandry and testing conditions, in addition to the intrinsic differences between the models. We have compared different HD models using standardized conditions to identify the most robust phenotypic differences, best suited for preclinical therapeutic efficacy studies. With a battery of tests of sensory-motor function, such as the open field and prepulse inhibition tests, we replicate previous results showing a strong and progressive behavioral deficit in the R6/2 line with an average of 129 CAG repeats in a mixed CBA/J and C57BL/6J background. We present the first behavioral characterization of a new model, an R6/2 line with an average of 248 CAG repeats in a pure C57BL/6J background, which also showed a progressive and robust phenotype. The BACHD in a FVB/N background showed robust and progressive behavioral phenotype, while the YAC128 full-length model on either an FVB/N or a C57BL/6J background generally showed milder deficits. Finally, the Hdh(Q111) knock-in mouse on a CD1 background showed very mild deficits. This first extensive standardized cross-characterization of several HD animal models under standardized conditions highlights several behavioral outcomes, such as hypoactivity, amenable to standardized preclinical therapeutic drug screening. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect