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

Pineal melatonin synthesis (serotonin --> N-acetylserotonin --> melatonin) is severely compromised in most inbred strains of mice, in many cases becau se serotonin is not acetylated by serotonin N-acetyltransferase (arylalkyla mine N-acetyltransferase, AANAT). We have found that in the C57BL/6J strain , AANAT mRNA encodes a severely truncated AANAT protein, because a pseudo-e xon 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 an d modify circadian rhythmicity. (C) 1998 Elsevier Science B.V. All rights r eserved.