Modeling complement-driven diseases in transgenic mice: Values and limitations

Immunobiology. 2016 Oct;221(10):1080-90. doi: 10.1016/j.imbio.2016.06.007. Epub 2016 Jun 16.

Abstract

Remarkable advances have been made over past decades in understanding the pathogenesis of complement-mediated diseases. This has led to development of new therapies for, and in some cases re-classification of, complement-driven diseases. This success is due to not only insight from human patients but also studies using transgenic animal models. Animal models that mimic human diseases are useful tools to understand the mechanism of disease and develop new therapies but there are also limitations due to species differences in their complement systems. This review provides a summary of transgenic animal models for three human diseases that are at the forefront of anti-complement therapy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). They are discussed here as examples to highlight the values and limitations of animal modeling in complement-driven diseases.

Keywords: C3G; Complement; PNH; Transgenic mouse; aHUS.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Atypical Hemolytic Uremic Syndrome / drug therapy
  • Atypical Hemolytic Uremic Syndrome / etiology
  • Atypical Hemolytic Uremic Syndrome / metabolism
  • Complement Activation / immunology
  • Complement Inactivating Agents / pharmacology
  • Complement Inactivating Agents / therapeutic use
  • Complement System Proteins / physiology*
  • Disease Models, Animal
  • Disease Susceptibility*
  • Hemoglobinuria, Paroxysmal / drug therapy
  • Hemoglobinuria, Paroxysmal / etiology
  • Hemoglobinuria, Paroxysmal / metabolism
  • Humans
  • Mice, Transgenic
  • Nephrosis / drug therapy
  • Nephrosis / etiology
  • Nephrosis / metabolism

Substances

  • Complement Inactivating Agents
  • Complement System Proteins