title: Role of subunit-9 of mitochondrial ATP synthase in Batten disease.
abstract: The role of subunit-9 of mitochondrial ATP synthase in Batten disease was defined by characterizing the expression of genes encoding this protein in human tissues. Two genetically distinct neuronal ceroid-lipofuscinoses (NCL) comprise Batten disease: the late-infantile (LINCL) and juvenile (JNCL) types. We tested cell lines and tissues from both types of patients, along with normal controls. Differences in expression between diseased and normal samples were found for both mRNA and protein. Antibody staining of subunit-9 protein was detected in LINCL and JNCL tissues, and in 6 LINCL and 4 of 5 JNCL fibroblast lines. No immunoreactivity was seen in fibroblasts from obligate carriers, normal controls, and 6 other storage disease controls, with the exception of faint staining in Niemann-Pick, type C cells. There was an appreciable difference in staining pattern in both tissue sections and fibroblasts between LINCL and JNCL. Three subunit-9 transcripts (Hum1, Hum2, and Hum3) were specifically detected in NCL and normal human tissue from heart, liver, brain, muscle, and pancreas. Transcriptional regulation of subunit-9 genes was found to be altered in Batten disease. Pseudogenes related to each of the subunit-9 genes were isolated. Sequence analysis of cDNAs spanning the protein-coding regions of the Hum1, Hum2, and Hum3 genes showed conclusively that the primary defect(s) causing NCL are not mutations in the protein-coding regions of the 3 known subunit-9 genes.
authors.affiliation: Department of Pediatric Neurology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Speier
authors.forename: W H
authors.initials: WH
authors.lastname: Qian
authors.forename: S
authors.initials: S
authors.lastname: Lane
authors.forename: A
authors.initials: A
authors.lastname: Cook
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: P
authors.initials: P
authors.lastname: Daniel
authors.forename: R M
authors.initials: RM
authors.lastname: Boustany
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002648:Child; D017931:DNA Primers; D005347:Fibroblasts; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D006580:Genetic Carrier Screening; D006801:Humans; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology*; D009542:Niemann-Pick Diseases / Q000201:enzymology; D016133:Polymerase Chain Reaction; D006180:Proton-Translocating ATPases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011544:Pseudogenes; D012016:Reference Values; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D046911:Macromolecular Substances; D006180:Proton-Translocating ATPases