contains an N-terminal signal peptide, a fibronectin type III domain, and a transmembrane domain. The 2 proteins share 60% identity in the FNIII domain and 86% in the transmembrane domain. Northern blot analysis of multiple mouse tissues detected highest expression of Fndc5 in adult brain and heart, and low expression in lung, skeletal muscle, and testis. Northern blot analysis of mouse embryonic mRNA first detected Fndc5
expression at embryonic day 11, with strongest expression at E15 and decreasing expression at E17. In situ hybridization demonstrated expression of Fndc5 in the fore- and midbrain, as well as in the brachial arches and the heart. Overexpression of a GFP-Fndc5 fusion protein in COS cells showed localization predominantly in the endoplasmic reticulum, with small amounts in the plasma membrane.