Natural melatonin ‘knockdown’ in C57BLr6J mice: rare mechanism

Ž . Pineal melatonin synthesis serotonin TM N-acetylserotonin TM melatonin is severely compromised in most inbred strains of mice, in Ž . many cases because serotonin is not acetylated by serotonin N-acetyltransferase arylalkylamine N-acetyltransferase, AANAT . We have found that in the C57BLr6J 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. q 1998 Elsevier Science B.V. All rights reserved.