A Gain-of-Function Mutation in Adenylate Cyclase 3 Protects Mice from Diet-Induced Obesity
Figure 2
A. Trace files from Adcy3 exon 3 sequencing of PCR products amplified from wild-type (WT, upper trace) and heterozygous Jll mutant (HET, lower trace) genomic DNA. The resulting amino acid sequences of wild-type and mutant Adcy3 proteins (amino acids 278ā280) are shown below the traces. Mutant position is marked with arrows. B. Alignment of all nine murine Adcy proteins in the region surrounding the Jll mutation (upper panel), and conservation of the affected methionine residue in vertebrate Adcy3 orthologs, but not in invertebrate ones (lower panel). Dots reflect weak amino acid similarity, colons similarity, and asterisks identity. Abbreviations used: Mm, mouse; Hs, human; Rn, rat; Am, honeybee; Dm, fruit fly. CāD. Mice heterozygous for Adcy3M279I in a backcrossed B6 background and fed a HFD display the expected Jll phenotypes. Male mice have lower body weight and fat mass (C), and both sexes show decreased body fat percent after 24 weeks on a HFD (D). All data are shown as mean +/ā SEM, * p<0.05, *** p<0.001 by Student's t-test.