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.
Nicholas Gekakis, San Diego State University
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.
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 Type||Chemically induced (ENU)|
|Allele Synonym(s)||Adcy3Jll-Gek; Adcy3M279I|
|Gene Symbol and Name||Adcy3, adenylate cyclase 3|
|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).|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the C57BL/6J-Adcy3Jll/GekJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #025690 in your Materials and Methods section.