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.
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, The Netherlands.
D A
DA
Evans
A A
AA
van der Kleij
M A
MA
Sonnemans
J P
JP
Burbach
F W
FW
van Leeuwen
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