Abstract
Dmbx1 is a paired-class homeodomain transcription factor of unknown function. To elucidate the physiological role, we generated mice deficient in Dmbx1 (Dmbx1−/− mice). Dmbx1−/− mice exhibit severe leanness associated with hypophagia and hyperactivity. To clarify the mechanism of their leanness, Dmbx1−/− mice were crossed with lethal yellow (Ay/a) mice, in which the ectopic expression of agouti protein causes marked obesity and diabetes mellitus associated with hyperphagia and insulin resistance. Interestingly, overexpression of agouti in Dmbx1−/− mice failed to induce the Ay/a phenotype. In Dmbx1−/− mice, administration of AgRP did not increase cumulative food intake over 24 and 48 h. In addition, Dmbx1 was shown to be expressed at E15.5 in lateral parabrachial nucleus (LPB), rostral nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMV), and reticular nucleus (RET) in the brain stem, all of which receive melanocortin signaling, indicating Dmbx1 participates in the development of the neural network for the signaling. Thus, Dmbx1 plays an important role in eliciting pleiotropic action of AgRP, regulating energy homeostasis and behavior. [J Physiol Sci. 2008;58 Suppl:S104]
