ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse.

The knockout (KO) of the adiponectin receptor 1 (AdipoR1) gene causes retinal degeneration. Here we report that ADIPOR1 protein is primarily found in the eye and brain with little expression in other tissues. Further analysis of AdipoR1 KO mice revealed that these animals exhibit early visual system abnormalities and are depleted of RHODOPSIN prior to pronounced photoreceptor death. A KO of AdipoR1 post-development either in photoreceptors or the retinal pigment epithelium (RPE) resulted in decreased expression of retinal proteins, establishing a role for ADIPOR1 in supporting vision in adulthood. Subsequent analysis of the Mfrprd6 mouse retina demonstrated that these mice are lacking ADIPOR1 in their RPE layer alone, suggesting that loss of ADIPOR1 drives retinal degeneration in this model. Moreover, we found elevated levels of IRBP in both the AdipoR1 KO and the Mfrprd6 models. The spatial distribution of IRBP was also abnormal. This dysregulation of IRBP hypothesizes a role for ADIPOR1 in retinoid metabolism.

Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma.

Lung mastocytosis and antigen-induced bronchoconstriction are common features in allergic asthmatics. It is therefore important that animal models of asthma show similar features of mast cell inflammation and reactivity to inhaled allergen. We hypothesized that house dust mite (HDM) would induce mastocytosis in the lung and that inhalation of HDM would trigger bronchoconstriction. Mice were sensitized with intranasal HDM extract, and the acute response to nebulized HDM or the mast cell degranulating compound 48/80 was measured with respiratory input impedance. Using the constant-phase model we calculated Newtonian resistance (Rn) reflecting the conducting airways, tissue dampening (G), and lung elastance (H). Bronchoalveolar lavage fluid was analyzed for mouse mast cell protease-1 (mMCP-1). Lung tissue was analyzed for cytokines, histamine, and α-smooth muscle actin (α-SMA), and histological slides were stained for mast cells. HDM significantly increased Rn but H and G remained unchanged. HDM significantly expanded mast cells compared with control mice; at the same time mMCP-1, α-SMA, Th2 cytokines, and histamine were significantly increased. Compound 48/80 inhalation caused bronchoconstriction and mMCP-1 elevation similarly to HDM inhalation. Bronchoconstriction was eliminated in mast cell-deficient mice. We found that antigen-induced acute bronchoconstriction has a distinct phenotype in mice. HDM sensitization caused lung mastocytosis, and we conclude that inhalation of HDM caused degranulation of mast cells leading to an acute bronchoconstriction without affecting the lung periphery and that mast cell-derived mediators are responsible for the development of the HDM-induced bronchoconstriction in this model.