Fig. 2

TMEM63A loss abolishes mechanosensitive currents in OLs and causes severe developmental hypomyelination (A) Wild-type Tmem63a (left; T63a+/+) and Tmem63a null allele with a genetic deletion of exons 15–17 (right; T63a−/−). (B) Cell-attached pressure clamp to record current in response to negative pressure on OL membrane. (C and D) Example traces of currents in response to graded mechanical stimulation ramps (10 mmHg steps) in T63a+/+ (C) and T63a−/− (D) non-responder and responder OLs. (E) Proportion of T63a+/+ vs. T63a−/− responder and non-responder OLs. (F) Pressure vs. current relationship for T63a+/+ responder OLs. (G–J) Half-maximal activation pressure (G), maximum peak current amplitude (H), activation time constant (I), and inactivation time constants (J) of T63a+/+ and T63a−/− responder OLs. (K–M) Left: coronal hemi-section (left) and higher magnification of boxed area (right) of a T63a+/+ (left hemi-section) and T63a−/− (right hemi-section) mouse brain immunostained for MBP at P11 (K), P21 (L), and P35 (M). Dotted line separates motor cortex (Cx), corpus callosum (CC), and striatum (Str). (N and O) Mean fluorescence intensity of MBP in the Cx (N) and CC (O). (P–R) High-magnification images of boxed areas in (K)–(M) (left) immunostained for ASPA. (S and T) ASPA+ cells per mm2 in the Cx (S) and CC (T). Data represent mean ± SEM. ns, non-significant; p > 0.05, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. See also Figures S3 and S5 and Table S3 (sample sizes and statistical tests).