Establishment of True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase Knockout Mice1–3

Abstract

AbstractPyridine nucleotide coenzymes are involved in >500 enzyme reactions and are biosynthesized from the amino acid L-tryptophan (L-Trp) as well as the vitamin niacin. Hence, “true” niacin-deficient animals cannot be “created” using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid (QA) phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected inqprt–/–mice. Theqprt+/+,qprt+/–, orqprt–/–mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. Whenqprt–/–mice were fed a complete diet, food intake and body weight gain did not differ from those of theqprt+/+andqprt+/–mice. On the contrary, in theqprt–/–mice fed the NiA-free diet, food intake and body weight were reduced to 60% (P< 0.01) and 70% (P< 0.05) of the corresponding values for theqprt–/–mice fed the complete diet at d 23, respectively. The nutritional levels of niacin, such as blood and liver NAD concentrations, were also lower in theqprt–/–mice than in theqprt+/+and theqprt+/–mice. Urinary excretion of QA was greater in theqprt–/–mice than in theqprt+/+andqprt+/–mice (P< 0.01). These data suggest that we generated truly niacin-deficient mice.