摘要：大多数退行性疾病最初是逐渐丧失特定类型的细胞，最后症状逐渐明显。比如说I型糖尿病，80%左右的胰岛B细胞丢失了，人体就会出现高血糖症状；再如帕金森，脑的神经细胞在特定的某个部分中所占的比例下降了70到80，人的运动功能就会出现障碍。因此提前阻止细胞的破损是至关重要的，但由于早期细胞损坏的研究模型限制，因此提前阻止细胞损害颇具挑战。
Most degenerative diseases begin with a gradual loss of specific cell types that progresses, eventually leading to symptoms. For example, in type I diabetes, hyperglycemia commonly develops when approximately 80 percent of the beta cells in the pancreas are lost; in Parkinson's disease, motor dysfunction typically begins when neurons in a certain portion of the brain are decreased by 70 to 80 percent. Finding ways to stop early cell destruction is vital, but methods to do so have proven challenging because of limitations of models for early stages of cell loss.
A research team led by Albert Edge, Ph.D., principal investigator at the Massachusetts Eye and Ear Infirmary's Eaton-Peabody Laboratory and associate professor at Harvard Medical School, have engineered a new mouse that that can be used for research on degenerative disease. Their paper describing the findings was published on May 16 in the Journal of Clinical Investigation.
The "Mos-iCsp3" mouse (for "mosaic inducible caspase 3 mouse") is engineered so that administration of a drug initiates destruction of cells in specifically designated tissues, explains Dr. Edge. Selection of the cell type to be killed is achieved by mating the Mos-iCsp3 mouse with a "Cre" mouse in which an enzyme called Cre recombinase is contained in selected tissues. Any cell that contains the enzyme begins to produce caspase 3. This protein, a so-called "cell death" protein, is subsequently kept in an inactive form until the mouse is treated with a drug that activates caspase 3. Upon treatment with the drug the selected cells die. Several hundred Cre mice exist and cover a broad array of cell types.
"The mouse provides a way to study degenerative diseases and a model organism in which to develop therapies for those diseases," Dr. Edge said. "We targeted inner ear hair cells, beta cells in the pancreas, and epidermal cells. We found that whereas the beta cells and skin cells showed some regeneration in response to cellular loss, inner ear hair cells were not capable of regeneration and thus hair cell death caused partial deafness. The mouse will expedite our efforts to replace inner ear cells lost in deafness."
