Fig. 1.

Ripk1^K376R/K376R mice die during embryogenesis. a Organization of the Ripk1^K376R mutant allele. Lysine (AAG) was mutated to Arginine (AGA) at the 376 position in RIPK1. The mutation was confirmed by sequencing. b Observed numbers of embryos or live born pups of the indicated genotypes at various developmental stages from Ripk1^K376R/+ mice intercrosses. Asterisk indicates the abnormal embryos. c Whole-mount dark field images of embryos with indicated genotypes. Images are representative of embryos from E10.5 (n = 5), E11.5 (n = 10), E12.5 (n = 16), E13.5 (n = 19), E14.5 (n = 5). d Representative Hematoxylin and eosin (H&E)-stained and TUNEL-stained fetal livers from mouse embryos of the indicated genotypes (Scale bars, 1 mm). Images are representative of fetal livers from wild-type (n = 3) and Ripk1^K376R/K376R (n = 3). Scale bars, 50 μm. e Immunostaining for VE-cad (green) and cleaved caspase-3(CC3) (red) on yolk sacs from wild-type and Ripk1^K376R/K376R embryos. Scale bars, 100 μm. Images are representative of embryos from E12.5 (n = 3/genotype). f The body samples from E12.5 embryos were analyzed by western blot and immunoblotted for PARP, CC3, p-RIPK1(S166), RIPK1, and RIPK3