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Updated: Sep 11, 2026
Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells
Published on: August 29, 2016
Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration
A L Lau1, T R Kumar, K Nishimori
1Departments of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
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.
Insights
Mice lacking activin betaC and betaE genes, which are expressed in the liver, showed no defects in liver development, function, or regeneration. These findings indicate activin betaC and betaE are not essential for liver health.
Area of Science:
- Hepatology and Molecular Biology
- Developmental Biology
- Genetics
Background:
- The liver performs vital functions including protein synthesis, nutrient storage, and detoxification.
- Negative regulators of liver growth are less understood than positive regulators.
- Transforming growth factor beta (TGF-beta) superfamily members like TGF-beta1 and activin A are known negative regulators of liver growth.
Purpose of the Study:
- To investigate the function of novel activin family members, specifically activin betaC and betaE.
- To determine the role of activin betaC and betaE in liver development, function, and regeneration.
Main Methods:
- Cloning and generation of mice deficient in activin betaC and betaE genes using gene targeting in embryonic stem cells.
- RNase protection assays to analyze gene expression patterns during embryonic development.
- Assessment of liver development, function, and regeneration after partial hepatectomy in mutant mice.
Main Results:
- Activin betaC and betaE genes are liver-specific in adult mice, with expression detected from embryonic day 11.5 and 17.5, respectively.
- Mice deficient in activin betaC and/or betaE were viable, fertile, and showed no abnormalities in liver development or function.
- Liver regeneration capacity in homozygous mutant mice after major partial hepatectomy was comparable to wild-type mice.
Conclusions:
- Activin betaC and activin betaE are not essential for embryonic development.
- These novel activin subunits do not play a critical role in the normal development, function, or regenerative capacity of the liver.
- The functions of activin betaC and betaE in adult mice remain to be elucidated, but they are not critical for liver homeostasis.
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