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Multiple defects and perinatal death in mice deficient in follistatin


FOLLISTATIN, an activin-binding protein and activin antagonist in vitro1,2, can bind to heparan sulphate proteoglycans3 and may function in vivo to present activins to their receptors. In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle4–11. In Xenopus laevis, over-expression of follistatin leads to induction of neural tissue12. Here we use loss-of-function mutant mice to investigate the function of follistatin in mammals. We find that follistatin-deficient mice are retarded in then* growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth. These defects are more widespread than those seen in activin-deficient mutant mice, indicating that follistatin may modulate the actions of several members of the transforming growth factor-β family.

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Matzuk, M., Lu, N., Vogel, H. et al. Multiple defects and perinatal death in mice deficient in follistatin. Nature 374, 360–363 (1995).

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