Mrc1 Xenograft-Applicable mouse models

Mrc1 corresponds to human MRC1 and encodes the mannose receptor CD206, a type I transmembrane endocytic lectin built from an N-terminal cysteine-rich domain that binds sulfated sugars, a fibronectin type II domain that binds collagen, and eight C-type lectin-like domains of which only a subset ligates terminal mannose, fucose, and N-acetylglucosamine in a calcium dependent manner. It functions constitutively in clathrin mediated uptake and lysosomal delivery, clearing circulating lysosomal hydrolases, thyroglobulin, and collagen fragments and shuttling glycosylated antigen for presentation, and it is expressed by tissue macrophages, lymphatic and hepatic sinusoidal endothelium, and tumor associated macrophages. Nulls are viable with elevated serum lysosomal enzymes, so the interesting alleles are usually reporter or Cre knockins for tracking and manipulating alternatively activated macrophages. Note that endothelial expression makes CD206 an imperfect macrophage restricted driver, and that Mrc2 and scavenger receptors share collagen internalization, so single deletion underestimates clearance.

Baseline Mrc1 loss or humanization may change engraftment. Pilot cohorts de risk larger studies.