BDNF transgene improves ataxic and motor behaviors in stargazer mice.
The stargazer (stg) mouse exhibits severe cerebellar ataxia, abnormal motor behavior, and absence epilepsy. Selective failure of cerebellar brain-derived neurotrophic factor (BDNF) expression is one of the molecular defects in stg mutant. To determine the in vivo effect of BDNF replacement on cerebellar function, we generated a double mutant line of stg-BDNF mice by crossbreeding BDNF-overexpressing transgenics with stg mutants. Significant upregulation of BDNF mRNA and protein levels was confirmed in the double mutant cerebellum. Gross examination showed less severe ataxia with normal cerebellar cytoarchitecture in stg-BDNF mice than the original stg mice. Behavioral characterization of stg-BDNF mice revealed significantly improved performance in swimming test and footprint analysis compared to stg mice. These results provide in vivo evidence for the correlation of the cerebellar BDNF levels to the ataxia and motor behaviors of stg mice.
Meng
Hongdi
H
Department of Ophthalmology, Pharmacology & Neuroscience, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA.
Larson
Sarah K
SK
Gao
Rui
R
Qiao
Xiaoxi
X
D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D001345:Autoradiography; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D011930:Reaction Time / Q000235:genetics; D013550:Swimming / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D012333:RNA, Messenger