Dmbx1 is essential in agouti-related protein action.
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.
Fujimoto
Wakako
W
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Shiuchi
Tetsuya
T
Miki
Takashi
T
Minokoshi
Yasuhiko
Y
Takahashi
Yoshihisa
Y
Takeuchi
Ayako
A
Kimura
Kazuhiro
K
Saito
Masayuki
M
Iwanaga
Toshihiko
T
Seino
Susumu
S
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
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