A congenic line of the C57BL/6J mouse strain that is proficient in melatonin synthesis

May 17, 2018Journal of pineal research

A C57BL/6J mouse strain that can produce melatonin

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Abstract

The C57BL/6J congenic line has acquired the capacity for rhythmic melatonin synthesis.

Melatonin synthesis is deficient in the C57BL/6J mouse strain due to nonfunctional genes responsible for key enzymes.
Functional alleles of the melatonin synthesis genes were introduced from the CBA/CaJ mouse strain to create the congenic line.
The new congenic line restores the melatonin-dependent rhythm of dopamine release in the retina.
Differences in the Aanat and Asmt genes between the CBA and B6 strains include single nucleotide polymorphisms and DNA segment variations.
This improved model organism may assist in studying melatonin's physiological functions across various scientific fields.

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The C57BL/6J (B6) is the most common inbred mouse strain used in biomedical research in the United States. Yet, this strain is notoriously known for being deficient in the biosynthesis of melatonin, an important effector of circadian clocks in the brain and in the retina. Melatonin deficiency in this strain results from nonfunctional alleles of the genes coding 2 key enzymes of the melatonin synthesis pathway: arylalkylamine-N-acetyltransferase (Aanat) and N-acetylserotonin-O-methyltransferase (Asmt). By introducing functional alleles of the Aanat and Asmt genes from the melatonin-proficient CBA/CaJ (CBA) mouse strain to B6, we have generated a B6 congenic line that has acquired the capacity of rhythmic melatonin synthesis. In addition, the melatonin-dependent rhythm of dopamine release in the retina is restored in the B6 congenic line. Finally, we have partially characterized the Aanat and Asmt genes of the CBA strain and have identified multiple differences between CBA and B6 alleles, including single nucleotide polymorphism and deletion/insertion of DNA segments of various sizes. As an improved model organism with functional components of the melatonin synthesis pathway and melatonin-dependent circadian regulations, the new line will be useful to researchers studying melatonin physiological functions in a variety of fields including, but not limited to, circadian biology and neuroscience. In particular, the congenic line will be useful to speed up introduction of melatonin production capacity into genetically modified mouse lines of interest such as knockout lines, many of which are on B6 or mixed B6 backgrounds. The melatonin-proficient B6 congenic line will be widely distributed.

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A congenic line of the C57BL/6J mouse strain that is proficient in melatonin synthesis

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