A research team studying mice discover those lacking GSK-3 beta die before birth, according to a Journal of Clinical Investigation article.

Women considering pregnancy who use lithium therapy for bipolar disorder should avoid new powerful drugs that inhibit glycogen synthase kinase 3 beta (GSK-3 b), say scientists studying whether GSK-3 proteins are important for heart development in mice.

Investigators at Thomas Jefferson University, Philadelphia, found that mice lacking GSK-3 b perish before delivery because loss of the protein target of lithium disrupts normal mouse embryonic heart progression, a development linking lithium therapy to congenital heart defects.

To determine the general role of GSK-3 kinases in mammalian heart development, and in particular the role of specific isoforms, scientists studied ES cells and mice deleted for either GSK-3a or GSK-3 b. While the GSK-3a–deficient embryos were born at the expected frequency and had no cardiac developmental defects, no live-born GSK-3b–deficient mice were recovered.

Some GSK-3 b embryos died of severe liver degeneration, but most died at the late stages of development. These embryos exhibited numerous defects in the heart, including thickening of the heart muscle due to increased proliferation of the heart muscle cells. The embryos also showed double outlet RV, ventricular septal defects, and hypertrophic myopathy, with near obliteration of the ventricular cavities.

The article appears in the Journal of Clinical Investigation.

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