Fig. 6. Renal hypoplasia or agenesis in Eya1/Six1 double heterozygous animals. (A-D) E17.5 wild type, Six1^+/- or Eya1^+/-/Six1^+/- kidneys. Samples shown in A, C and D were X-gal stained for Six1^lacZ and it is expressed in the testis (t) and muscles surrounding the ureters and kidneys (D). Eya1^+/-/Six1^+/- animals show either smaller kidneys bilaterally (A), a small kidney on one side and no kidney on the other side (B), or complete absence of kidneys (C,D). In some Eya1^+/-/Six1^+/- animals that show renal agenesis, ureters that end blindly are observed (arrow in B,C). Adrenal glands and the genital tracts appeared to be normal in all compound heterozygous animals analyzed so far. (E,F) Histological analysis of kidneys of E17.5 Six1^+/- and Eya1^+/-/Six1^+/- animals. The number of nephrons was markedly reduced in the double heterozygous kidneys, but normal developing structures are present. The lower panels are higher magnification of the boxed areas. In Six1^+/- animals, the differentiating metanephric cap tissue (vesicles) in the peripheral nephrogenic zone, in which ureteric bud branching and induction of new nephrons takes place, are morphologically apparent (arrow in E). However, in the hypoplastic Eya1^+/-/Six1^+/- kidney, the differentiating metanephric vesicles in the peripheral nephrogenic zone were largely reduced in number (arrow in F). (G,H) A reduced number of ureteric bud branches is detected in the compound heterozygous animals at E13.5. ct, convoluting tubule; g, glomerulus; ur, ureter.

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