Figure 1
From: Irx3 is required for postnatal maturation of the mouse ventricular conduction system
Loss of Irx3 leads to abnormal electrical activation of the ventricles and morphological defects of the VCS.
(a,b) Representative surface ECG traces show QRS prolongation and notched R’ wave in 10–12 week old Irx3−/−;Cx40+/EGFP mice (b) compared to Irx3+/+;Cx40+/EGFP mice (a–d). Optical mapping results in the apical four-chamber view. Isochrone lines with 0.5 ms intervals mark areas where depolarization reached 50% intensity. Irx3+/+;Cx40+/EGFP hearts show simultaneous electrical breakthroughs in both LV and RV with depolarization proceeding in an apex-to-base direction, whereas Irx3−/−;Cx40+/EGFP hearts show a breakthroughs only present in left ventricle (LV) and lack in right ventricle (RV), suggestive of RBB block. (e–j) Fluorescence images of the VCS visualized using 10–12 week old adult mice expressing Cx40-promoter driven EGFP (Cx40+/EGFP). Compared to Irx3+/+;Cx40+/EGFP mice (e,g,i), Irx3−/−;Cx40+/EGFP mice show reduced fiber densities and fluorescence intensity in the VCS of the left ventricle (f) and right ventricular septal and free walls (RSW and RVFW, respectively) (h,j). The morphology of the VCS was further compared between Irx3+/LacZ and Irx3−/LacZ mice. In Irx3+/LacZ heart, β-gal staining of Irx3 expressing cells marked His-Purkinje system in LV (k) RSW (m) and RVFW (o). On the other hand, VCS morphology of Irx3−/LacZ heart was severely compromised in LV (l) RSW (n) and RVFW (p) with reduced number and density of fibers in bundle branches and distal Purkinje fiber networks. As marked by a red arrowhead (n’), RBB of Irx3−/LacZ heart is found disconnected in many cases. k’,l’,m’,n’ illustrate magnification of framed in panels. HB, His-bundle; LBB, left bundle branch; DF, distal fiber; RBB, right bundle branch; SA, septal artery; and PF, Purkinje fibers.
