C57BL/6J-Adcy3^Jll/GekJ

Stock number: 025690

Description

This ENU mutagenesis generated point mutation of Adcy3 results in a hyperactive allele, Jll, and is useful in studies of diet induced obesity, energy homeostasis, and cAMP signaling.

Detailed description

The Adcy3 gene encodes for a Ca2+-calmodulin-sensitive adenylate cyclase that catalyzes cAMP formation. These mice carry a chemically induced (ENU) point mutation of Adcy3: a G-to-A transition at base 827, M279I. The Jll allele is hyperactive compared to the wildtype allele, and is dominantly inherited. After 8 weeks on a high fat diet, heterozgous mice on the C57BL/6 background exhibit lower body weights and fat mass (absolute and relative) than wildtype controls. Heterozygotes on the B6;129 background also have lower fasting plasma leptin and plasma insulin levels than wildtype controls. Homozygous mice on both the B6;129 and C57BL/6 backgrounds exhibit a phenotype similar to that seen in heterozygotes. Mice that are homozygous for the targeted mutation (B6;129 and C57BL/6 backgrounds) are viable and fertile.

Development

This point mutation was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males. Mutagenized males were backcrossed to C57BL/6J females for 8 generations. The mutation results in a G to A transition at base position 827 of the Adcy3 transcript. The mutation alters the corresponding amino acid 279 from methionine-to-isoleucine. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Adcy3^Jll
Name: Jll
MGI accession ID: MGI:5574448
Generation method: Chemically induced (ENU)
Marker symbol: Adcy3
Marker name: adenylate cyclase 3
Chromosome: 12
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced a G to A transition that results in the amino acid substitution of methionine-to-isoleucine at position 279 (M279I).