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Retinal gene expression of low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice

ABSTRACT: Retinal gene expression was assessed from postnatal day (P) 8 old low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice with a Illumina mouse-WG6 expression BeadChip.

ORGANISM(S): Mus musculus

PROVIDER: GSE32145 | GEO | 2012/05/22

SECONDARY ACCESSION(S): PRJNA147657

REPOSITORIES: GEO

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Retinal gene expression of low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice

Project description:Retinal gene expression was assessed from postnatal day (P) 8 old low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice with a Illumina mouse-WG6 expression BeadChip. RNA was extracted from the retinas of P8 Lrp5 knockout and wild type mice (n=3 each group). Total RNA (1ug each) were reverse transcribed, followed by a single in vitro transcription amplification to incorporate biotin-labeled nucleotide, and subsequent hybridization and staining with strepatavidin-Cy3 according to the manufacturer’s instructions.

2012-05-21 | E-GEOD-32145 | biostudies-arrayexpress

Differential gene expression analysis of eys+/-; lrp5+/- zebrafish eye by microarray

Project description:Vision is essential for vertebrates including humans. Sustained vision is accomplished by retinoid metabolism, the ‘visual cycle’, where all-trans retinol (atROL) is incorporated into the retinal pigment epithelium (RPE) from photoreceptors presumably through decade-long missing receptor(s). Here, we show that the LDL-related receptor-5 (Lrp5) protein is linked to the retinol binding protein 1a (Rbp1a), the transporter of atROL in the visual cycle, by generating and analyzing the digenic eyes shut homolog+/-; lrp5+/- zebrafish, the same form of gene defect detected in a human case of inherited retinal degeneration. Global gene expression analysis followed by genetic study clarified that rbp1a played a role downstream of lrp5. Rbp1a protein was colocalized with Lrp5 protein at microvilli of RPE cells. Furthermore, Rbp1a directly bound to the C-terminal intracellular region of Lrp5 in vitro. Collectively, these results strongly suggest that Lrp5 is a potent candidate of the receptor of atROL in the visual cycle.

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Low-density lipoprotein receptor-5 contributes to whole body metabolism by regulating fatty acid metabolism in the osteoblast

Project description:Wnt signaling is critical for normal skeletal development as well as whole-body metabolic function. In this study, we described a previously unrecognized function for Wnt-Lrp5 signaling in the osteoblast that allows bone to acquire the resources necessary to fuel bone formation. Mice lacking the Lrp5 co-receptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass and also develop peripheral adiposity with corresponding reductions in energy expenditure. Conversely, mice expressing a high-bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not Lrp6, regulate the expression of key enzymes required for fatty acid β-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate-specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism Total RNA isolated from cultures of Lrp5-deficient osteoblasts differentiated for 7 days in vitro compared to control osteoblasts

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Low-density lipoprotein receptor-5 contributes to whole body metabolism by regulating fatty acid metabolism in the osteoblast

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Retinal expression of Wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice.

Project description:Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout (Lrp5(-/-)) mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing Lrp5(-/-) mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from Lrp5(-/-) and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in Lrp5(-/-) retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in Lrp5(-/-) retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in Lrp5(-/-) retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR.

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