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Fig. 7. Reducing Spry1 dosage in Itga8-null embryos rescues kidney development. (A) Graph illustrating the average number of kidneys per animal at birth in animals of the genotypes indicated. Note that the percent agenesis is significantly reduced in Itga8^-/-;Spry1^+/- versus Itga8^-/-;Spry1^+/+ animals (P<0.005; see legend to Table 1). The rescue of kidney development was complete in Itga8^-/-;Spry1^-/- animals. However, we found the proportion of Itga8^-/-;Spry1^-/- animals that demonstrated a duplicated ureter phenotype did not appear to differ from the proportion of their Spry1^-/- littermates displaying that phenotype (Bason et al., 2005). (B,C) Transverse sections through embryonic kidneys of the genotypes indicated, stained with hematoxylin and eosin. Note the characteristic lack of invasion of the MM by the UB (arrowhead) at E11.5 in an Itga8^-/-;Spry1^+/+ embryonic kidney. The UB has invaded the MM at E11.5 in an Itga8^-/-;Spry1^+/- embryonic kidney. (D-G) Transverse sections through embryonic kidneys of the genotypes indicated, showing expression at E11.5 of Gdnf and Eya1, as detected by in situ hybridization. (D,E) Note the substantial reduction in the level of Gdnf expression in the MM of the Itga8^-/-;Spry1^+/- mutant compared with that in the control (Itga8^+/-;Spry1^+/-) embryo, despite invasion of the UB into the MM (arrowhead). Arrows point to Gdnf expression in the limb buds, which is similar in both genotypes. (F,G) Eya1 expression is similar in Itga8^-/-;Spry1^+/- and control (Itga8^+/-;Spry1^+/-) embryos. Note invasion of the UB into the MM of the Itga8^-/-;Spry1^+/- and control (Itga8^+/-;Spry1^+/-) embryos (arrowheads). Scale bars: 50 µm.

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