Heterozygous Weaver mice showed postnatal overgrowth. CRISPR/Cas9 genome editing was used to generate a mouse model carrying a Weaver-associated Ezh2 variant (V626M). (A) Crosses of heterozygotes generated mice that were wild-type, heterozygous, or homozygous for the Weaver variant, which was confirmed by PCR amplification of a genomic region containing the variant followed by Sanger sequencing. (B) Body weight was measured in heterozygous Weaver mice and wild-type (WT) littermates weekly up until 8 weeks of age (homozygotes were perinatally lethal). Two-way analysis of variance (ANOVA) showed that body weights differed significantly between genders and genotypes (both P < 0.001). Pairwise comparison showed that, in both males (M) and females (F), body weights were significantly increased in heterozygous Weaver mice. (C–H) At 8 weeks of age, heterozygote Weaver mice showed increased weights of heart, kidney, and spleen but no differences in weights of liver and lung or in tibia length compared with wild-type mice. *P < 0.05.