title: Dmbx1 is essential in agouti-related protein action.
abstract: Dmbx1 is a paired-class homeodomain transcription factor. We show here that mice deficient in Dmbx1 exhibit severe leanness associated with hypophagia and hyperactivity and that isolation of a Dmbx1(-/-) mouse from its cohabitants induces self-starvation, sometimes leading to death, features similar to those of anorexia nervosa in humans. Interestingly, overexpression of agouti in Dmbx1(-/-) mice failed to induce aspects of the A(y)/a phenotype, including hyperphagia, obesity, and diabetes mellitus. In Dmbx1(-/-) mice, administration of agouti-related protein increased cumulative food intake for the initial 6 h but significantly decreased it over 24- and 48-h periods. In addition, Dmbx1 was shown to be expressed at embryonic day 15.5 in the lateral parabrachial nucleus, the rostral nucleus of the tractus solitarius, the dorsal motor nucleus of the vagus, and the reticular nucleus in the brainstem, all of which receive melanocortin signaling, indicating involvement of Dmbx1 in the development of the neural network for the signaling. Thus, Dmbx1 is essential for various actions of agouti-related protein and plays a role in normal regulation of energy homeostasis and behavior.
authors.affiliation: Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Fujimoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Minokoshi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Ayako
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D005247:Feeding Behavior; D018507:Gene Expression Regulation, Developmental; D007031:Hypothalamus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D009479:Neuropeptides / Q000737:chemistry; D051857:Otx Transcription Factors / Q000235:genetics* / Q000502:physiology*; D010641:Phenotype; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D051857:Otx Transcription Factors; C470836:Otx3 protein, mouse