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Updated: Jul 16, 2026
Preparation of 3D Decellularized Matrices from Fetal Mouse Skeletal Muscle for Cell Culture
Published on: March 3, 2023
Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development
Xianghua Zhou1, Fei Tian, Johan Sandzén
1Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Göteborg University, SE 413 45 Göteborg, Sweden.
Abstract:
Mutations in filamin B (FLNB), a gene encoding a cytoplasmic actin-binding protein, have been found in human skeletal disorders, including boomerang dysplasia, spondylocarpotarsal syndrome, Larsen syndrome, and atelosteogenesis phenotypes I and III. To examine the role of FLNB in vivo, we generated mice with a targeted disruption of Flnb. Fewer than 3% of homozygous embryos reached term, indicating that Flnb is important in embryonic development. Heterozygous mutant mice were indistinguishable from their wild-type siblings. Flnb was ubiquitously expressed; strong expression was found in endothelial cells and chondrocytes. Flnb-deficient fibroblasts exhibited more disorganized formation of actin filaments and reduced ability to migrate compared with wild-type controls. Flnb-deficient embryos exhibited impaired development of the microvasculature and skeletal system. The few Flnb-deficient mice that were born were very small and had severe skeletal malformations, including scoliotic and kyphotic spines, lack of intervertebral discs, fusion of vertebral bodies, and reduced hyaline matrix in extremities, thorax, and vertebrae. These mice died or had to be euthanized before 4 weeks of age. Thus, the phenotypes of Flnb-deficient mice closely resemble those of human skeletal disorders with mutations in FLNB.
Insights
Filamin B (FLNB) is crucial for embryonic development, as Flnb gene disruption in mice led to severe skeletal and vascular defects. These findings link FLNB mutations to human skeletal disorders.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Mutations in filamin B (FLNB) are associated with several human skeletal dysplasias.
- FLNB is a cytoplasmic actin-binding protein involved in cytoskeletal organization.
Purpose of the Study:
- To investigate the in vivo function of FLNB during embryonic development.
- To elucidate the role of FLNB in skeletal and vascular development.
Main Methods:
- Generation of Flnb-deficient mice using targeted gene disruption.
- Analysis of embryonic lethality, skeletal morphology, and microvasculature development.
- Assessment of Flnb-deficient fibroblast function, including actin organization and migration.
Main Results:
- Homozygous Flnb disruption resulted in embryonic lethality, with <3% of embryos reaching term.
- Flnb-deficient embryos showed impaired microvasculature and skeletal development.
- Born Flnb-deficient mice exhibited severe skeletal malformations and reduced viability.
- Flnb-deficient fibroblasts displayed disorganized actin filaments and impaired migration.
Conclusions:
- FLNB is essential for embryonic development, particularly for skeletal and vascular systems.
- Flnb deficiency in mice recapitulates phenotypes of human skeletal disorders caused by FLNB mutations.
- FLNB plays a critical role in maintaining cellular structure and function, impacting tissue development.
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