Miki Terakata, Tsutomu Fukuwatari, Mitsue Sano, Natsuki Nakao, Ryuzo Sasaki, Shin-Ichi Fukuoka, Katsumi Shibata
Department of Food Science and Nutrition, School of Human Cultures, University of Shiga Prefecture, Hassakacho, Hikone, Shiga, Japan.
The Journal of nutrition 2012 DecPyridine 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 in qprt(-/-)mice. The qprt(+/+), qprt(+/-), or qprt(-/-) 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. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and qprt(+/-) mice. On the contrary, in the qprt(-/-) 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 the qprt(-/-) 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 the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of QA was greater in the qprt(-/-) mice than in the qprt(+/+) and qprt(+/-) mice (P < 0.01). These data suggest that we generated truly niacin-deficient mice.
Miki Terakata, Tsutomu Fukuwatari, Mitsue Sano, Natsuki Nakao, Ryuzo Sasaki, Shin-Ichi Fukuoka, Katsumi Shibata. Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice. The Journal of nutrition. 2012 Dec;142(12):2148-53
PMID: 23096007
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