title: The mouse Clc1/myotonia gene: ETn insertion, a variable AATC repeat, and PCR diagnosis of alleles.
abstract: Myotonias are muscle diseases in which the function of the muscular chloride channel ClC-1 is impaired. Null alleles of the corresponding Clc1 gene on mouse chromosome (Chr) 6 provide animal models for human myotonias. It was shown that the allele adr (Clc1adr) is due to an insertion of an ETn type transposon that is transcribed and leads to multiple splicing events; the allele mto (Clc1adr-mto) involves a stop codon near the N-terminus. We have determined the genomic organization of the mouse Clc1 gene and the sequence requirements for the transposon insertion in the Clc1adr allele. The mouse Clc1 gene is composed of 23 exons, ranging from 39 to 372 bp, and spans approximately 23 kb of genomic DNA. The exon/intron organization is highly homologous to that of the human CLCN1 gene; the homology of the coding sequence is 97% to rat and 89% to human. In the adr allele the ETn transposon is inserted into intron 12, the largest intron. Whereas the 5' and 3' LTR sequences of the ETn transposon are homologous to those reported for other insertional mutations of the mouse, no consensus motif for an insertion target site could be defined. On the basis of flanking sequences, we provide duplex PCR diagnoses for the adr, adr-mto, and wild-type alleles of Clc1. Close to the 3' end of intron 12, a tetranucleotide repeat (AATC)n was found that is polymorphic between mouse species Mus musculus, M. molossinus, M. castaneus, and M. spretus, and can thus be used for chromosomal mapping studies.
authors.affiliation: Developmental Biology Unit, University of Bielefeld, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Schnülle
authors.forename: O
authors.initials: O
authors.lastname: Antropova
authors.forename: M
authors.initials: M
authors.lastname: Gronemeier
authors.forename: N
authors.initials: N
authors.lastname: Wedemeyer
authors.forename: H
authors.initials: H
authors.lastname: Jockusch
authors.forename: J W
authors.initials: JW
authors.lastname: Bartsch
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels / Q000235:genetics*; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements; D005091:Exons; D005796:Genes / Q000235:genetics*; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009222:Myotonia / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D017385:Sequence Homology
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D004251:DNA Transposable Elements; D009124:Muscle Proteins; D004247:DNA