Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system
J. Clin. Invest. Patrick Y. Jay, et al. 113:1130 doi:10.1172/JCI19846 [Go to this article.]

Figure 1
The absence of the AV node primordium in Nkx2-5–null mutant embryos. (A) Schematic diagram of the Nkx2-5 genomic structure, targeting construct, and Nkx2-5^neo allele and Northern blot analysis demonstrating a 50% reduction in Nkx2-5 mRNA in the Nkx2-5^+/neo adult ventricular myocardium. (B) WT Nkx2-5 E9.5 embryos that carry the minK-lacZ gene show blue X-gal staining in the inner curvature of the AV canal (arrow). (C) Nkx2-5^neo/neo E9.5 embryos show abnormal development of the heart tube and no minK-lacZ activity in the AV canal region where the AV node primordium is expected (arrow); staining is normal in the somites (arrowhead). In situ hybridization for minK mRNA and the corresponding brightfield images demonstrate expression throughout the myocardium of WT (D and E) and Nkx2-5^neo/neo (F and G) embryos. All images are representative of three or more embryos or mice. Comparisons of minK-lacZ expression were made between animals with identical copy numbers of the reporter allele. B and C show minK-lacZ homozygotes; heterozygotes yield similar results. WT, Nkx2-5 WT; Het, Nkx2-5^+/neo; KO, Nkx2-5^neo/neo; H, HindIII; N, NotI; S, SpeI; e 1, exon; e 2, exon 2; L, loxP sequence; neo, pGK neomycin resistance cassette. Probe denotes fragments used for Southern blot analysis. Scale bars: 200 μm (B and C), 100 μm (D–G).