A: Cyp26A1 mRNA levels are significantly elevated in the livers of 3-month-old male chow-fed CrbpI−/− (n = 5), Lrat−/− (n = 5), and Lrat−/−/CrbpI−/− (L/C−/−) (n = 7) mice compared with age- and gender-matched WT (n = 6) mice. mRNA levels were determined in triplicate for each liver by qPCR. Expression levels are normalized for hepatic expression of 18S rRNA. Statistical significance: a, P < 0.01 compared with WT mice. B: Rarβ2 mRNA levels are significantly elevated in the same livers from Lrat−/− and Lrat−/−/CrbpI−/− (L/C−/−) mice compared with WT mice. mRNA levels were determined in triplicate for each liver by qPCR. Expression levels are normalized for hepatic expression of 18S rRNA. Statistical significance: a, P < 0.05 compared with WT mice. C: Serum and liver all-trans-RA concentrations are significantly lower for Lrat−/− (n = 9) compared with WT (n = 9) mice. Statistical significance: a, P < 0.01 compared with WT mice. D: A representative LC/MS/MS profile for RA for an extract obtained for a 3-month-old male Lrat−/− liver showing the multiple reaction monitoring peaks due to all-trans-RA (at-RA, retention time 8.29 min) and penta-deuterated all-trans-RA (at-RA-d5, retention time 8.22 min) employed as the internal standard. E: Fragmentation spectra for authentic all-trans-RA standard (upper spectrum) and for the endogenous all-trans-RA detected in an Lrat−/− liver extract (lower spectrum).