Document Type

Article

Publication Date

Fall 10-4-2013

Abstract

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in development of Alzheimer’s disease. Often, members of this diverse family of receptors perform overlapping roles in the same tissues, complicating the analysis of their function through conventional targeted mutagenesis. Here, we describe development of a mouse Mesd (Mesoderm Development) conditional knockout allele, and demonstrate that ubiquitous deletion of Mesdusing Cre-recombinase blocks gastrulation, as observed in the traditional knockout and albino-deletion phenotypes. This conditional allele will serve as an excellent tool for future characterization of the cumulative contribution of LRP members in defined tissues.

Comments

Published PLoS ONE 8(10): e75782. doi: http://dx.doi.org/10.1371/journal.pone.0075782

Funding: These studies were supported in part by National Institutes of Health grant to BCH (GM53964) and to Drs. Robert Haltiwanger and BCH (CA123071). Adenovirus was produced by the Stony Brook University Stem Cell Core Facility funded by NYSTEM (C026716). No additional external funding was received for this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: Bernadette Holdener is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

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