Establishment of True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase Knockout Mice  

Oleh:

Terakata, Miki ; Fukuwatari, Tsutomu ; Sano, Mitsue ; Nakao, Natsuki

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 142 no. 12 (Dec. 2012), page 2148-2153.
Topik: Methodology and Mathematical Modeling

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2012.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Pyridine 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.

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