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. 2013 Oct 15;123(11):4875–4887. doi: 10.1172/JCI69781

Figure 5. MMF treatment interacts with Ret and Sox10 mutations to increase penetrance and severity of HSCR-like pathology.

Figure 5

(A and D) MPA treatment in 24-hour explant cultures revealed that neither Ret nor Sox10 heterozygosity affected BrdU incorporation. (B and E) In contrast, Ret but not Sox10 heterozygosity reduced ENCDC migration distance, and MPA treatment had an additive effect on ENCDC migration distance. Interaction terms were not statistically significant. (C and F) Pregnant dams were provided MMF or control PBS in drinking water, and the ENS was examined at E18.5 with neuronal fiber (TuJ1) and soma (HuC/HuD) markers. The position of the most caudal soma within the intestine is plotted as a dot, and the region of hypoganglionosis is plotted as a line. Mean positions of aganglionosis are denoted by black lines. Groups without abnormal fetuses are summarized as 1 dot and number. Treatment with MMF from E7.5 to E18.5 resulted in hypoganglionosis and aganglionosis with genotype-dependant penetrance and severity. Treatment with MMF from E9.5 to E14.5 demonstrated genotype-dependent reversal of the MMF-induced developmental delays. ***P < 0.001, 2-way ANOVA (A, B, D, and E).