Nonsense and missense mutations in the muscular chloride channel gene Clc-1 of myotonic mice
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::689fa65d5f514c2bc50fc9cc059d3e00 http://europepmc.org/abstract/med/8119941 |
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| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....689fa65d5f514c2bc50fc9cc059d3e00 |
| Autor: | Tj Jentsch, A Condie, Monika Gronemeier, Klaus Steinmeyer, J Prosser, Harald Jockusch |
| Předmět: |
DNA
Complementary Molecular Sequence Data Mice Inbred Strains Biology medicine.disease_cause Biochemistry Myotonia Mice Chloride Channels Genotype medicine Animals Humans Missense mutation Amino Acid Sequence Allele Molecular Biology Gene Genetics Mutation Base Sequence Sequence Homology Amino Acid Muscles Wild type Cell Biology medicine.disease Molecular biology Stop codon |
| Zdroj: | Europe PubMed Central |
| Popis: | In mature vertebrate muscle, the chloride channel Clc-1 is necessary for the stabilization of the resting potential. Its functional defect leads to the disease myotonia. The ADR mouse (phenotype ADR, genotype adr/adr) is an animal model for human myotonias. The adr gene is a member of a family of non-complementing recessive autosomal mutations (''alleles'' of adr) that cause myotonia in the mouse. The standard allele adr has arisen by the insertion of a retroposon into the chloride channel gene Clc-1 (Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., and Jentsch, T. J. (1991) Nature 354, 304-308). In order to study the nature of two other alleles, adr(mto) and adr(K), we have analyzed overlapping Clc-1 cDNA amplification products by the hydroxylamine and osmium tetroxide modification technique and direct sequencing. A comparison between ADR*MTO and C57BL/6 wild type showed six base pair substitutions, one of which resulted in a stop codon in position 47, whereas the five others are either silent or lead to amino acid substitutions in non-conserved regions of the Clc-1 sequence and were already present in the wild type inbred SWR/J strain from which adr(mto) was derived. The detection of the stop codon in the adr(mto) allele is further indication of the identity of the Clc-1 chloride channel with the adr myotonia gene in the mouse, because a chain termination close to the N terminus would necessarily destroy gene function. For the ethylnitrosourea-induced mutation adr(K), an Ile --> Thr exchange in codon 553 was identified. As this affects a conserved residue within a highly conserved region of the Clc-1 gene, a functional significance of this residue is suggested. |
| Databáze: | OpenAIRE |
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