title: Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice.
abstract: 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.
authors.affiliation: Department of Food Science and Nutrition, School of Human Cultures, University of Shiga Prefecture, Hassakacho, Hikone, Shiga, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Terakata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuwatari
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sano
authors.forename: Natsuki
authors.initials: N
authors.lastname: Nakao
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sasaki
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shibata
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004435:Eating; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009243:NAD / Q000378:metabolism; D009525:Niacin / Q000172:deficiency*; D009536:Niacinamide / Q000652:urine; D010430:Pentosyltransferases / Q000172:deficiency* / Q000378:metabolism; D017378:Quinolinic Acid / Q000652:urine; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
chemical_list: D009243:NAD; D009536:Niacinamide; D009525:Niacin; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid