ABSTRACT
A missense mutation in the human alpha synuclein gene was recently identified in some cases of familial Parkinson's disease (FPD). We have developed an antibody that recognizes the C-terminal 12 amino acids of the human alpha synuclein protein and have demonstrated that alpha synuclein is an abundant component of the Lewy bodies found within the degenerating neurons of patients with Parkinson's disease (PD). The presence of alpha synuclein in Lewy bodies of sporadic PD patients suggests a central role for alpha synuclein in the pathogenesis of PD.
Subject(s)
Brain/pathology , Lewy Bodies/pathology , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/genetics , Parkinson Disease/genetics , Parkinson Disease/pathology , Substantia Nigra/pathology , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Amino Acid Sequence , DNA Primers , Dementia/pathology , Exons , Female , Humans , Male , Middle Aged , Mutation, Missense , Nerve Tissue Proteins/immunology , Neurites/pathology , Neurons/pathology , Peptide Fragments/chemistry , Peptide Fragments/immunology , Phosphoproteins/analysis , Synucleins , alpha-SynucleinSubject(s)
Chromosomes, Human, Pair 7/genetics , DNA-Binding Proteins , Nerve Tissue Proteins/genetics , Transcription Factors/genetics , Zinc Fingers/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , Cloning, Molecular , DNA, Complementary/genetics , Gene Expression , Humans , Molecular Sequence Data , Sequence Homology, Amino AcidSubject(s)
Chromosome Mapping , Chromosomes, Human, Pair 19 , Gene Expression Regulation, Developmental , Nerve Tissue Proteins/genetics , Transcription Factors , Zinc Fingers/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary , Evolution, Molecular , Hippocampus , Humans , Molecular Sequence Data , Sequence Homology, Amino AcidABSTRACT
We report the cloning and characterization of a novel cDNA termed C2H2-546 which encodes a C2H2-type zinc finger protein. C2H2-546 RNA is expressed in the HTLV-1 infected T cells examined which were derived from HAM-TSP patients, but not in T cells derived from ATL patients. The C2H2-546 gene is conserved in humans and primates and maps to chromosome 10q11.2, a site associated with a variety of cancers. Thus, C2H2-546 is a candidate regulatory molecule important in the formation of these tumors, and may serve as an important marker to distinguish HTLV-1 infected ATL versus HAM-TSP T cell lineages.
Subject(s)
Chromosomes, Human, Pair 10/genetics , Gene Expression Regulation, Viral , Genes , HTLV-I Infections/genetics , Human T-lymphotropic virus 1/physiology , Neoplasm Proteins/genetics , T-Lymphocytes/metabolism , Zinc Fingers/genetics , Amino Acid Sequence , Animals , Base Sequence , Chromosomes, Artificial, Yeast , DNA, Complementary/genetics , Drosophila melanogaster/genetics , Humans , Kruppel-Like Transcription Factors , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/pathology , Mammals/genetics , Molecular Sequence Data , Neoplasm Proteins/biosynthesis , Nuclear Proteins , Paraparesis, Tropical Spastic/genetics , Paraparesis, Tropical Spastic/pathology , Polymerase Chain Reaction , Saccharomyces cerevisiae/genetics , Species Specificity , T-Lymphocytes/virology , Transcription Factors , Tumor Cells, CulturedABSTRACT
Ecm1, the mouse gene encoding extracellular matrix protein 1, is highly expressed in bone and cartilage as well as in osteogenic, preosteoblastic and chondroblastic cell lines. Ecm1 was recently localized to a chromosomal region in mouse syntenic to human chromosome 1q21, establishing this gene as a prime candidate gene for pycnodysostosis, a rare, autosomal recessive sclerosing skeletal dysplasia. Shortly thereafter, it was determined that cathepsin K is the pycnodysostosis gene. We now report the radiation hybrid mapping of human ECM1 to 1q21, and the gene structure and coding sequence of human ECM1.