BAC to degeneration bacterial artificial chromosome (BAC)-mediated transgenesis for modeling basal ganglia neurodegenerative disorders.
Basal ganglia neurodegenerative disorders, such as Parkinson's disease (PD) and Huntington's disease (HD), are characterized by not only spectrum of motor deficits, ranging form hypokinesia to hyperkinesia, but also emotional, cognitive, and psychiatric manifestations. The symptoms and pathogenic mechanism of these disorders should be viewed as dysfunctions of specific cortico-subcortical neurocircuits. Transgenic approaches using large genomic inserts, such as bacterial artificial chromosome (BAC)-mediated transgenesis, due to its capacity to propagate large-size genomic DNA and faithful production of endogenous-like gene expression pattern/lever, have provided an ideal basis for the generation of transgenic mice as model for basal ganglia neurodegenerative disorders, as well as the functional and structural analysis of neurocircuits. In this chapter, the basic concepts and practical approaches about application of BAC transgenic system are introduced. Existent major BAC transgenic mouse models for PD and HD are evaluated according to their construct, face, and predicative validity. Finally, considerations, possible solutions, and future perspectives of using BAC transgenic approach to study basal ganglia neurodegenerative disorders are discussed.
Lu
Xiao-Hong
XH
Department of Psychiatry & Biobehavioral Sciences, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
D000818:Animals; D001480:Basal Ganglia Diseases / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology