Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.
Mutations in DNA underlie carcinogenesis, inherited pathology, and aging and are generally thought to be introduced during meiosis and mitosis. Here we report that in post-mitotic neurons specific frameshift mutations occur at high frequency. These mutations were identified in vasopressin transcripts in magnocellular neurons of the homozygous Brattleboro rat and predominantly consist of a GA deletion in GAGAG motifs. Immunocytochemistry provides evidence for similar events in wild-type rats. However, the diseased state of the Brattleboro rat, resulting in a permanent activation of vasopressin neurons, enhanced the mutational rate. These data reveal hitherto unrecognized somatic mutations in nondividing neurons.
Evans
D A
DA
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, The Netherlands.
van der Kleij
A A
AA
Sonnemans
M A
MA
Burbach
J P
JP
van Leeuwen
F W
FW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008938:Mitosis; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014667:Vasopressins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*
D017931:DNA Primers; D014667:Vasopressins