Isx participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15'-monooxygenase (Bcmo1) expression.
Isx (intestine specific homeobox) is an intestine-specific transcription factor. To elucidate its physiological function, we generated Isx-deficient mice by knocking in the beta-galactosidase gene (LacZ) in the Isx locus (IsxLacZ/LacZ mice). LacZ staining of heterozygous (IsxLacZ/+) mice revealed that Isx was expressed abundantly in intestinal epithelial cells from duodenum to proximal colon. Quantitative mRNA expression profiling of duodenum and jejunum showed that beta-carotene 15,15'-monooxygenase (EC1.14.99.36 Bcmo1) and the class B type I scavenger receptor, which are involved in vitamin A synthesis and carotenoid uptake, respectively, were drastically increased in IsxLacZ/LacZ mice. Although mild vitamin A deficiency decreased Isx expression in duodenum of wild-type (Isx+/+) mice, severe vitamin A deficiency decreased Isx mRNA expression in both duodenum and jejunum of Isx+/+ mice. On the other hand, vitamin A deficiency increased Bcmo1 expression in both duodenum and jejunum of Isx+/+ mice. However, Bcmo1 expression was not increased in duodenum of IsxLacZ/LacZ mice by mild vitamin A deficiency. These data suggest that Isx participates in the maintenance of vitamin A metabolism by regulating Bcmo1 expression in the intestine.
Seino
Yusuke
Y
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Miki
Takashi
T
Kiyonari
Hiroshi
H
Abe
Takaya
T
Fujimoto
Wakako
W
Kimura
Keita
K
Takeuchi
Ayako
A
Takahashi
Yoshihisa
Y
Oiso
Yutaka
Y
Iwanaga
Toshihiko
T
Seino
Susumu
S
D000818:Animals; D004386:Duodenum / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000235:genetics / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
C527930:Isx protein, mouse; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014157:Transcription Factors; D019207:beta Carotene; D014801:Vitamin A; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase