Fig. 2. The Grem1 deficiency causes neonatal lethality because of complete bilateral renal agenesis and lung defects in combination with distal limb defects. (A,B) Urogenital defects in Gre^ORF homozygous newborn mice. Mutant mice display complete bilateral agenesis of the kidney (ki) and ureter (ur). Note that gonads (go) and adrenal glands (ad) form correctly, while the bladder (bl) is not filled in mutant mice. (C-F) Lung defects in newborn Grem1-deficient mice. (C,D) Transversal histological sections through the lung of newborn wild-type mouse (C) and Grem1-deficient mouse (D) at the level of the heart. (E,F) High-magnification views of a longitudinal section through the lungs of a wild-type (E) and a Grem1-deficient (F) newborn mice. av, alveoli; bl, bronchiole. (G-J) Limb skeletal abnormalities in Gre^ORF homozygous newborn mice; (G,H) forelimbs, (I,J) hindlimbs. Arrows indicate the zeugopod; arrowheads indicate metacarpal bones. Digit numbers are reduced and identities lost in Gre^ORF/ORF limbs. Asterisk indicates a fused digit 1; question marks indicate posterior digits with unclear identities.