Natural melatonin 'knockdown' in C57BL/6J mice: rare mechanism truncates serotonin N-acetyltransferase

Brain Res Mol Brain Res. 1998 Dec 10;63(1):189-97. doi: 10.1016/s0169-328x(98)00273-3.

Abstract

Pineal melatonin synthesis (serotonin --> N-acetylserotonin --> melatonin) is severely compromised in most inbred strains of mice, in many cases because serotonin is not acetylated by serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT). We have found that in the C57BL/6J strain, AANAT mRNA encodes a severely truncated AANAT protein, because a pseudo-exon containing a stop codon is spliced in. This is the first identification of a natural mutation which knocks down melatonin synthesis. The decrease in melatonin signaling may have been a selective factor in the development of laboratory strains of mice because melatonin can inhibit reproduction and modify circadian rhythmicity.

MeSH terms

  • Animals
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / metabolism
  • Blotting, Northern
  • Brain / enzymology
  • Circadian Rhythm / genetics
  • DNA, Complementary / analysis
  • Gene Expression Regulation, Enzymologic*
  • Introns / genetics
  • Melatonin / genetics*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout / physiology*
  • Molecular Sequence Data
  • Pineal Gland / enzymology*
  • RNA Splicing / genetics
  • RNA, Messenger / analysis
  • Recombinant Proteins / genetics
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Recombinant Proteins
  • Arylamine N-Acetyltransferase
  • Melatonin

Associated data

  • GENBANK/AF004108
  • GENBANK/AF004109
  • GENBANK/AF004110
  • GENBANK/AF004111
  • GENBANK/U83462