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 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.
Roseboom
P H
PH
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Namboodiri
M A
MA
Zimonjic
D B
DB
Popescu
N C
NC
Rodriguez
I R
IR
Gastel
J A
JA
Klein
D C
DC
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology; D002940:Circadian Rhythm / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D007438:Introns / Q000235:genetics; D008550:Melatonin / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D008969:Molecular Sequence Data; D010870:Pineal Gland / Q000201:enzymology*; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin