The liver is an essential organ that produces several serum proteins, stores vital nutrients, and detoxifies many carcinogenic and xenobiotic compounds. Various growth factors positively regulate liver growth, but only a few negative regulators are known. Among the latter are the transforming growth factor β (TGF-β) superfamily members TGF-β1 and activin A. To study the function of novel activin family members, we have cloned and generated mice deficient in the activin βC and βE genes. Expression analyses demonstrated that these novel genes are liver specific in adult mice. Here, we show by RNase protection that activin βC transcripts are present in the liver beginning at embryonic day 11.5 (E11.5) whereas activin βE expression is detected starting from E17.5. Gene targeting in embryonic stem ceils was used to generate mice with null mutations in either the individual activin βC and βE genes or both genes. In contrast to the structurally related activin βA and βB subunits, which are necessary for embryonic development and pituitary follicle-stimulating hormone homeostasis, mice deficient in activin βC and βE were viable, survived to adulthood, and demonstrated no reproductive abnormalities. Although activin βC and βE mRNAs are abundantly expressed in the liver of wild-type mice, the single and double mutants did not show any defects in liver development and function. Furthermore, in the homozygous mutant mice, liver regeneration after >70% partial hepatectomy was comparable to that in wild-type mice. Our results suggest that activin βC and βE are not essential for either embryonic development or liver function.
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