Rabbit Anti-Human VLDLR (a.a. 418-722) Polyclonal antibody

Objective: To identify and characterize biochemical alterations in the retinas of very low-density lipoprotein receptor ( VLDLr) knockout mice in an animal model of retinal angiomatous proliferation. Methods: Immunohistochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and electrophoretic mobility shift assay were used to identify and characterize the altered gene and protein expression as well as signal cascades involved in the pathogenesis of neovascularization in the retinas of VLDLr mice. Results: Expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor was significantly greater in the lesion area, and Muller cells around the lesion area were activated, as indicated by increased expression of glial fibrillary acidic protein. Expression of the proinflammatory cytokine IL-18 ( interleukin 18) and the inflammation mediator intercellular adhesion molecule-1 was increased before significant intraretinal neovascularization. Furthermore, phosphorylation of Akt and mitogen-activated protein kinase and translocalization of nuclear factor kappa B were greater in VLDLr knockout mouse retinas. Conclusion: An inflammatory process is involved in the development of neovascularization in the VLDLr knockout mouse retina. Clinical Relevance: Understanding the molecular mechanisms underlying these biochemical alterations in the retinas of VLDLr knockout mice will provide a foundation for developing novel therapeutic approaches to retinal angiomatous proliferation.

We studied the postnatal development of the radial glial scaffold in the dentate gyrus of reeler mice, lacking the extracellular matrix protein Reelin, in scrambler mice, deficient in the intracellular adaptor protein disabled1 (Dab1), which is required for the transmission of the Reelin signal into the cell, and in mutant mice lacking the Reelin receptors apolipoprotein receptor 2 (ApoER2) and/or the very low density lipoprotein receptor (VLDLR), known to transmit the Reelin signal via Dab1. By immunolabeling for the glial fibrillary acidic protein (GFAP), we show that a regular dentate radial glial scaffold fails to form in mutants deficient of Reelin, Dab1, and VLDLR and ApoER2. Mutant mice lacking only one of the Reelin receptors, VLDLR or ApoER2, display a gradual expression of the radial glial defects seen in mutants that lack both receptors. Our results suggest that Reelin signaling via ApoER2, VLDLR, and Dab1 is required for the formation of a regular radial glial scaffold in the dentate gyrus. (C) 2003 Wiley-Liss, Inc.