(A) Schematic representation of WT TAK1 and kinase domain-truncated (green) TAK1 protein. (B) Treatment protocol for tamoxifen-induced Cre recombination in Tak1^mKO mice. Six-week-old Tak1^fl/fl and Tak1^mKO mice were given i.p. injections of tamoxifen, and 3 weeks later, the mice were analyzed. (C) Gross appearance of Tak1^fl/fl and Tak1^mKO mice. (D) Average body weight of Tak1^fl/fl and Tak1^mKO mice. (E) Average forelimb and (F) average 4-paw grip strength in Tak1^fl/fl and Tak1^mKO mice normalized by their body weight. (G) Representative images of skinned Tak1^fl/fl and Tak1^mKO mice. Arrow pointing to kyphotic phenotype in Tak1^mKO mice. (H) Average weight of soleus (Sol), gastrocnemius (GA), tibialis anterior (TA), quadriceps (Quad), and extensor digitorum longus (EDL) muscles in Tak1^fl/fl and Tak1^mKO mice. (I) Representative photomicrographs of TA muscle sections of Tak1^fl/fl and Tak1^mKO mice after staining for H&E (top panel) and anti-laminin (lower panel). Scale bars: 20 μm. Quantification of (J) average myofiber CSA, and (K) mean minimal Feret’s diameter in TA and soleus muscle sections of Tak1^fl/fl and Tak1^mKO mice. (L) PCR analysis of genomic DNA from GA muscle of tamoxifen-treated Tak1^fl/fl and Tak1^mKO mice using primer sets that detect truncated TAK1 and TNF receptor 1 (TNFR1). Representative PCR gel images presented here demonstrate efficient deletion of the kinase domain of TAK1 in Tak1^mKO mice following tamoxifen administration. (M) Immunoblots presented here demonstrate that the protein levels of TAK1, but not TAB1 or TRAF6, were diminished in GA muscle of Tak1^mKO mice. n = 6 or 7 in each group. Error bars represent ± SEM. *P < 0.05, values significantly different from corresponding Tak1^fl/fl mice by unpaired 2-tailed t test.