UCLA Advance Will Enable Deeper Insights into Astrocyte Function & Possibly Increased Understanding of ALS & Other Neurological Disorders

An achievement by UCLA neuroscientists could lead to a better understanding of astrocytes, a type of cell in the brain that is thought to play a role in Lou Gehrig’s disease (also called amyotrophic lateral sclerosis, or ALS); Alzheimer’s disease; Huntington’s disease; and other neurological disorders. The researchers are the first to have bred mice in which an artificial gene called Cre/ERT2, a basic tool for studying the functions of cells, can be activated exclusively in astrocytes. A paper describing their work was published online on December 8, 2016 in the journal Neuron. The article is titled “New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo.” Neuroscientists have been trying for years to engineer mice in which Cre/ERT2 or other artificial genes can be activated just in astrocytes without significant “leakage” into other cell types. “We’ll now be able to delete or mutate astrocyte genes that are suspected of contributing to diseases such as ALS to see whether they really do contribute,” said Baljit Khakh, Ph.D., Professor of Physiology and Neurobiology at the David Geffen School of Medicine at UCLA. “That, in turn, could open up many new strategies for treating those diseases.” To give the mice the Cre/ERT2 gene, Dr. Khakh and colleagues inserted it into another gene, Aldh1-l1. Aldh1-I1 had been found in a previous study to only be active in adult astrocytes. Cre/ERT2 normally can be activated in mice by giving them a drug called tamoxifen, which is best known as a breast cancer treatment. The UCLA researchers, however, built the combination gene so that tamoxifen could only “turn on” the Cre/ERT2’s when it was in astrocytes.
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