Blood-Brain Barrier Defects Associated with Rbp9 Mutation

• Published in: Molecules and cells 2010, 29(1), , pp.93-98
• Main Authors: Kim, J.H., Sejong University, Seoul, Republic of Korea, Kim, Y.J., Yonsei University, Seoul, Republic of Korea, Ha, J.S., Sejong University, Seoul, Republic of Korea
• Format: Article
• Language: English
• Subjects: adhesion; Animals; Animals, Genetically Modified; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; blood brain barrier; Blood-Brain Barrier - abnormalities; Blood-Brain Barrier - metabolism; Carcinoma, Small Cell - genetics; Carcinoma, Small Cell - physiopathology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Biology; Disease Models, Animal; DROSOPHILA; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; elav; Gene Expression Profiling; Humans; Inteins - genetics; Life Sciences; Longevity - genetics; Lung Neoplasms - genetics; Lung Neoplasms - physiopathology; Motor Activity - genetics; Mutagenesis, Site-Directed; Mutant Proteins - genetics; Mutant Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Paraneoplastic Syndromes, Nervous System; Protein Binding; Rbp9; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-010-0040-0

Rbp9 is a Drosophila RNA-binding protein that shares a high level of sequence similarity with Drosophila elav and human Hu proteins. Loss of function alleles of elav are embryonic lethal causing abnormal central nervous system (CNS) development, and Hu is implicated in the development of paraneoplastic neurological syndrome associated with small cell lung cancer. To elucidate the role of Rbp9, we generated Rbp9 mutant flies and examined them for symptoms related to paraneoplastic encephalomyelitis. Although Rbp9 proteins begin to appear from the middle of the pupal period in the cortex of the CNS, the Rbp9 mutants showed no apparent defects in development. However, as the mutant adult flies grew older, they showed reduced locomotor activities and lived only one-half of the life expectancy of wild-type flies. To understand the molecular mechanism underlying this symptom, gene expression profiles in Rbp9 mutants were analyzed and potential target genes were further characterized. Reduced expression of cell adhesion molecules was detected, and defects in the blood-brain barrier (BBB) of Rbp9 mutant brains could be seen. Putative Rbp9-binding sites were found in introns of genes that function in cell adhesion. Therefore, Rbp9 may regulate the splicing of cell adhesion molecules, critical for the formation of the BBB.