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Published on: October 27, 2020
Functional analysis of mammalian members of the transforming growth factor-beta superfamily
1The Departments of Pathology, Cell Biology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Analysis of growth factor function has come from studies both in vitro and in vivo. However, the generation of mice deficient in a specific growth factor via gene targeting (for example, "knockout") strategies in embryonic stem (ES) cells will often evaluate the essential roles of the protein in vivo and, in many cases, discover new functions. In this review, studies to date are discussed on the generation and analysis of mice deficient in members of the transforming growth factor (TGF-beta) superfamily. Among the genes targeted via ES cell strategies are the TGF-beta1, Müllerian-inhibiting substance (MIS), inhibin alpha, activin betaA, and activin betaB genes. In addition, the mouse short ear and brachypodism mutants and insertional mutant 413-d have been identified as mutations in the BMP-5, GDF-5, and nodal loci, respectively. These studies have led to critical insights into the functions of these gene products and have further emphasized the importance of members of the TGF-beta superfamily in mammalian development, reproduction, and oncogenesis.
Insights
Gene targeting in mice reveals essential roles for transforming growth factor-beta (TGF-beta) superfamily members in development and disease. These studies uncover new functions for growth factors in mammals.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Growth factor function is studied in vitro and in vivo.
- Gene targeting in embryonic stem (ES) cells is a powerful tool to evaluate protein roles.
- The transforming growth factor-beta (TGF-beta) superfamily plays crucial roles in biological processes.
Purpose of the Study:
- To review studies on the generation and analysis of mice deficient in TGF-beta superfamily members.
- To highlight the insights gained from these studies into growth factor functions.
- To emphasize the importance of TGF-beta superfamily members in mammalian biology.
Main Methods:
- Gene targeting (knockout) strategies in ES cells.
- Analysis of mice deficient in specific TGF-beta superfamily genes (e.g., TGF-beta1, MIS, inhibin alpha, activin betaA, activin betaB).
- Identification and analysis of naturally occurring mouse mutants (short ear, brachypodism, insertional mutant 413-d) linked to specific loci (BMP-5, GDF-5, nodal).
Main Results:
- Successful generation and analysis of mice deficient in various TGF-beta superfamily members.
- Identification of mutations in BMP-5, GDF-5, and nodal loci in specific mouse mutants.
- Demonstration of critical roles for these gene products in vivo.
Conclusions:
- Studies on gene-targeted mice have provided critical insights into TGF-beta superfamily functions.
- Members of the TGF-beta superfamily are essential for mammalian development.
- These growth factors are also implicated in reproduction and oncogenesis.
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