(A) TyrBap1 KO (KO) mice gained weight more slowly than Bap1^fl/wt Tyr-Cre⁺ heterozygous (Het) and WT littermates. Points indicate mean weight. Linear regression and 95% confidence interval are shown. (B) TyrBap1 KO mice (right) were smaller than WT (left) or heterozygous (not shown) littermates. A representative P20 TyrBap1 KO mouse had visible abdominal distention (white arrows). (C) TyrBap1 KO died early (median survival 20 days, n = 37). Only mice left with parents and soft moist food lived beyond P25. (D) Most TyrBap1 KO had an abnormal colon by P15, with increased severity as age increased. (E) P15 WT typically had well-formed stool pellets in mid- and distal colon (arrows). (F) P15 TyrBap1 KO colon was often deformed in ways never seen in controls. Black arrowhead highlights twisted and stiff mid-colon. The more proximal colon (white arrowhead) and distal small intestine (black arrow) accumulated loose feces. (G) TyrBap1 KO colon and distal small intestine became severely distended owing to aggregated feces later in life. Representative P27 TyrBap1 KO bowel. (H) Feces accumulated in the distal small intestine (DSI) of TyrBap1 KO, increasing with age (30.4% at P15 and 88.9% at >P20). (I) White fur spots were common on TyrBap1 KO abdomen (white arrow) indicating incomplete melanocyte colonization (P10 mouse). (J) Quantitative analysis of incomplete skin colonization by melanocytes. (A–J) KO refers to Bap1^fl/fl Tyr-Cre⁺, Het refers to Bap1^fl/wt Tyr-Cre⁺, and WT refers to Bap1^wt/wt Tyr-Cre⁺ genotype, except in A, where WT includes Bap1^wt/wt Tyr-Cre⁺ and mice lacking Cre. ****P < 0.0001. (A) Repeated-measures 1-way ANOVA. (C) Log-rank (Mantel-Cox) test. (J) Two-tailed binomial test.