Cldn2/12 DKO mice have hypocalcemia, hypercalciuria, and decreased intestinal Ca2+ absorption. (A) Serum-ionized Ca2+ (median ± interquartile range [IQR], n = 10 WT, 13 DKO, Mann–Whitney U Test, and P = 0.002). (B) Ca2+ bioavailability as a percent of Ca2+ consumed (mean ± SD, n = 23 WT, 24 DKO, Student’s t test, and P = 0.001). (C) Fractional excretion of urinary Ca2+ normalized to WT for each genotype (median ± IQR, n = 10 WT, 12 DKO, 11 Cldn2 WT, 13 Cldn2 KO, Mann–Whitney U test, P < 0.0001 WT versus DKO, P = 0.003 Cldn2 WT versus KO, and P = 0.011 DKO versus Cldn2 KO). (D) Net 3 d Ca2+ balance (mean ± SD, n = 19 WT, 18 DKO, Student’s t test, and P = 0.043). (E) Serum PTH levels (mean ± SD, n = 22 WT, 25 DKO, Student’s t test, and P = 0.039). (F) Serum calcitriol (median ± IQR, n = 17 WT, 17 DKO, Mann–Whitney U Test, and P = 0.099). *P < 0.05.