Humanized mice for immune system investigation: progress, promise and challenges.
ABSTRACT Significant advances in our understanding of the in vivo functions of human cells and tissues and the human immune system have resulted from the development of 'humanized' mouse strains that are based on severely immunodeficient mice with mutations in the interleukin-2 receptor common γ-chain locus. These mouse strains support the engraftment of a functional human immune system and permit detailed analyses of human immune biology, development and functions. In this Review, we discuss recent advances in the development and utilization of humanized mice, the lessons learnt, the remaining challenges and the promise of using humanized mice for the in vivo study of human immunology.
- SourceAvailable from: Kadriye Nehir Cosgun[Show abstract] [Hide abstract]
ABSTRACT: In-depth analysis of the cellular and molecular mechanisms regulating human HSC function will require a surrogate host that supports robust maintenance of transplanted human HSCs in vivo, but the currently available options are problematic. Previously we showed that mutations in the Kit receptor enhance engraftment of transplanted HSCs in the mouse. To generate an improved model for human HSC transplantation and analysis, we developed immune-deficient mouse strains containing Kit mutations. We found that mutation of the Kit receptor enables robust, uniform, sustained, and serially transplantable engraftment of human HSCs in adult mice without a requirement for irradiation conditioning. Using this model, we also showed that differential KIT expression identifies two functionally distinct subpopulations of human HSCs. Thus, we have found that the capacity of this Kit mutation to open up stem cell niches across species barriers has significant potential and broad applicability in human HSC research.Cell Stem Cell 07/2014; 15(2). DOI:10.1016/j.stem.2014.06.001 · 22.15 Impact Factor
Article: A brief history of animal modeling.[Show abstract] [Hide abstract]
ABSTRACT: Comparative medicine is founded on the concept that other animal species share physiological, behavioral, or other characteristics with humans. Over 2,400 years ago it was recognized that by studying animals, we could learn much about ourselves. This technique has now developed to the point that animal models are employed in virtually all fields of biomedical research including, but not limited to, basic biology, immunology and infectious disease, oncology, and behavior.Missouri medicine 110(3):201-5.
- Missouri medicine 110(3):206.