INTR10

Authors:

Raber KA 1
Urbach YK 1
Stephan M 2
Nguyen HP 3
Riess O 3
von Horsten S 1

Institutions:

1 Franz-Penzoldt-Center, Section of Experimental Therapy, University of Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany
2 Dept. of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
3 Dept. of Medical Genetics, University of Tuebingen, Calwerstr. 7, 72076 Tuebingen, Germany

Title of abstract : early detection of a behavioral phenotype in rats transgenic for huntington’s disease

Abstract text:

Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disorder caused by CAG repeat expansion in the huntingtin gene. The transgenic rat model (tgHD) carrying a truncated human huntingtin fragment of 51 CAG repeats under control of the rat Htt promoter closely resembles the late-onset form of HD exhibiting the earliest aggregates at about 6 months of age. It has been shown that behavioral symptoms precede the appearance of aggregates in this model.
To further study this early behavioral phenotype in tgHD rats we performed ultrasonic vocalization, acoustic startle response, and prepulse inhibition tests in P10-17 pups. To study exploration and risk behavior the novel cage test was performed in pre-weaning 21 days old rats. In this test each animal was allowed to explore a clean cage for five minutes. Early exploration and risk taking were determined.
Exploration and risk taking were greatly altered in pre-weaning rats. Homozygous transgenic rats exhibit increased free rearing behavior and spent more time in the center and less time in the wall area of the cage compared to wild type rats. Furthermore, transgenic P10 rat pups emitted significantly less ultrasonic calls, which were also of shorter duration. Testing of sensory motor gaiting revealed a loss of prepulse inhibition at day 17 already.
Gene expression profiling and qrtPCR confirmation on P10 pups striata revealed changes in at least 8 behavior-associated genes.
These data suggest that the tgHD rat could be a useful model in treatment studies due to the early behavioral phenotype detectable at day 10 and day 21.

This entry was posted on Wednesday, August 20th, 2008 at 15:43 and is filed under HD: clinical applications, all. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.