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Publication : Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation.

First Author  Fujioka M Year  2011
Journal  J Clin Invest Volume  121
Issue  6 Pages  2462-9
PubMed ID  21576819 Mgi Jnum  J:173515
Mgi Id  MGI:5014214 Doi  10.1172/JCI45081
Citation  Fujioka M, et al. (2011) Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation. J Clin Invest 121(6):2462-9
abstractText  Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic beta cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies.
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