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Göteborgs universitets publikationer

Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development

Författare och institution:
Xianghua Zhou (Wallenberglaboratoriet & Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Fei Tian (Wallenberglaboratoriet); Johan Sandzen (Wallenberglaboratoriet); R. Cao (-); E. Flaberg (-); L. Szekely (-); Y. Cao (-); Claes Ohlsson (Institutionen för medicin, avdelningen för invärtesmedicin); Martin Bergö (Wallenberglaboratoriet); Jan Borén (Wallenberglaboratoriet); Levent Akyürek (Wallenberglaboratoriet & Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi)
Publicerad i:
Proc Natl Acad Sci U S A, 104 ( 10 ) s. 3919-24
0027-8424 (Print)
Artikel, refereegranskad vetenskaplig
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Actins/metabolism, Animals, Bone and Bones/*physiology, Cell Movement, Chondrocytes/metabolism, Contractile Proteins/deficiency/*genetics/*physiology, Cytoplasm/metabolism, Endothelial Cells/metabolism, Fibroblasts/metabolism, Humans, Kyphosis/genetics, Mice, Mice, Knockout, *Microcirculation, Microfilament Proteins/deficiency/*genetics/*physiology, Scoliosis/genetics
Postens nummer:
Posten skapad:
2007-09-27 14:34
Posten ändrad:
2011-01-20 10:00

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