Pros and Cons of Reconstitution Models

There are several advantages to reconstitution models. (1) In the reconstituted tissue, the oncogene expressing cells proliferate in a mixture with normal cells, which mimics tumor growth in humans. (2) The reconstitution procedure itself restricts expression of oncogenes to specific cell types. Therefore, any ubiquitous promoter can be used to drive the expression of the oncogenes, whereas tissue-specific promoters are needed in establishing transgenic models. (3) The stroma environment can be modified by choosing specific mouse strains as recipient mice. (4) Early or mild lesions can be observed and propagated through reconstitution. (5) Mammary or prostate glands can be rescued from mutant mice with a lethal phenotype. (For example, Brca2ASH/ASH mutant mice start to die at around birth, yet, the MECs of those mice can be collected from E15.5 embryos and used in reconstitution.) (6) This system allows the implantation ofdonor cells into isogenic hosts, thereby retaining the dynamic interaction of the immune system with the tumor.

The disadvantage of this system is that each reconstitution has to be established surgically. Therefore, it is not suitable for the production of large numbers of mice, limiting their utility in the drug discovery process to late-stage preclinical characterization of development candidates. These models are also applicable in testing the efficacy of lead compounds.

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