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Updated: Jun 12, 2026
Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes
Published on: February 13, 2021
Inactivation of Palb2 gene leads to mesoderm differentiation defect and early embryonic lethality in mice
Pia Rantakari1, Jenni Nikkilä, Heli Jokela
1Department of Physiology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland.
Abstract:
Mutations of the PALB2 tumor suppressor gene in humans are associated with hereditary predisposition to breast and also some other cancers. In the present study, we have characterized mice deficient in Palb2. The data show that the Palb2((+/-)) mice are normal and fertile, and lack macroscopic tumors when followed up till the age of 8 months. Homozygous (HO) Palb2((-/-)) mice present with embryonic lethality and die at E9.5 at the latest. The mutant embryos are smaller in size, developmentally retarded and display defective mesoderm differentiation after gastrulation. In Palb2((-/-)) embryos, the expression of cyclin-dependent kinase inhibitor p21 is increased, and Palb2((-/-)) blastocysts show a growth defect in vitro. Hence, the phenotype of the Palb2((-/-)) mice in many regards resembles those previously reported for Brca1 and Brca2 knockout mice. The similarity in the phenotypes between Palb2, Brca1 and Brca2 knockout mice further supports the functional relationship shown in vitro for these three proteins. Accordingly, our data in vivo suggest that a key function for PALB2 is to interact with and to build up appropriate communication between BRCA1 and BRCA2, thereby licensing the successful performance of the physiological tasks mediated by these two proteins, particularly in homologous recombination and in proper DNA damage response signaling.
Insights
Loss of the PALB2 gene causes embryonic lethality in mice, similar to BRCA1 and BRCA2. This highlights PALB2's crucial role in DNA repair and tumor suppression.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Mutations in the tumor suppressor gene PALB2 are linked to hereditary breast and other cancers.
- Understanding the in vivo function of PALB2 is crucial for comprehending its role in cancer predisposition.
Purpose of the Study:
- To characterize the in vivo phenotype of mice deficient in Palb2.
- To investigate the functional relationship between PALB2, BRCA1, and BRCA2 in DNA damage response.
Main Methods:
- Generation and analysis of Palb2 heterozygous ((+/-)) and homozygous ((-/-))) knockout mice.
- Phenotypic characterization of mutant embryos and blastocysts, including developmental assessments and gene expression analysis.
Main Results:
- Palb2((+/-)) mice are normal and do not develop tumors by 8 months.
- Homozygous Palb2((-/-)) mice exhibit embryonic lethality by E9.5, with smaller, developmentally retarded embryos showing defective mesoderm differentiation.
- Palb2((-/-)) embryos display increased p21 expression and blastocysts show in vitro growth defects.
Conclusions:
- The phenotype of Palb2((-/-)) mice closely resembles that of Brca1 and Brca2 knockout mice, supporting a functional link.
- PALB2 is essential for embryonic development, likely by facilitating the interaction and communication between BRCA1 and BRCA2.
- These findings underscore PALB2's critical role in homologous recombination and DNA damage response, similar to BRCA1 and BRCA2.
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