Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration.
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 beta (TGF-beta) superfamily members TGF-beta1 and activin A. To study the function of novel activin family members, we have cloned and generated mice deficient in the activin betaC and betaE genes. Expression analyses demonstrated that these novel genes are liver specific in adult mice. Here, we show by RNase protection that activin betaC transcripts are present in the liver beginning at embryonic day 11.5 (E11.5) whereas activin betaE expression is detected starting from E17.5. Gene targeting in embryonic stem cells was used to generate mice with null mutations in either the individual activin betaC and betaE genes or both genes. In contrast to the structurally related activin betaA and betaB subunits, which are necessary for embryonic development and pituitary follicle-stimulating hormone homeostasis, mice deficient in activin betaC and betaE were viable, survived to adulthood, and demonstrated no reproductive abnormalities. Although activin betaC and betaE 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 betaC and betaE are not essential for either embryonic development or liver function.
Departments of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
A L
AL
Lau
T R
TR
Kumar
K
K
Nishimori
J
J
Bonadio
M M
MM
Matzuk
D028341:Activins; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D017353:Gene Deletion; D007265:Inhibins / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice
D028341:Activins; D007265:Inhibins