{"id":4346,"date":"2023-01-25T19:51:34","date_gmt":"2023-01-25T18:51:34","guid":{"rendered":"http:\/\/www.sfbmec.fr\/?p=4346"},"modified":"2023-01-25T19:51:44","modified_gmt":"2023-01-25T18:51:44","slug":"the-critical-role-of-the-tb5-domain-of-fibrillin-1-in-endochondral-ossification","status":"publish","type":"post","link":"http:\/\/www.sfbmec.fr\/?p=4346","title":{"rendered":"The critical role of the TB5 domain of fibrillin-1 in endochondral ossification"},"content":{"rendered":"

F\u00e9licitations \u00e0 l’\u00e9quipe de Carine Le Goff (INSERM U1148, Laboratory of Vascular Translational Science, Bichat Hospital, Paris, Universit\u00e9 Paris Cit\u00e9) et ses collaborateurs pour leur derni\u00e8re publication dans Human Molecular Genetics !<\/p>\n

Laure Delhon, Zakaria Mougin, J\u00e9r\u00e9mie Jonquet, Ang\u00e9lique Bibimbou, Johanne Dubail, Cynthia Bou-Chaaya, Nicolas Goudin, Wilfried Le Goff, Catherine Boileau, Val\u00e9rie Cormier-Daire, Carine Le Goff, The critical role of the TB5 domain of fibrillin-1 in endochondral ossification,\u00a0Human Molecular Genetics<\/em>, Volume 31, Issue 22, 15 November 2022, Pages 3777\u20133788,\u00a0https:\/\/doi.org\/10.1093\/hmg\/ddac131<\/a><\/p>\n

Mutations in the fibrillin-1 (FBN1<\/em>) gene are responsible for the autosomal dominant form of geleophysic dysplasia (GD), which is characterized by short stature and extremities, thick skin and cardiovascular disease. All known\u00a0FBN1<\/em>\u00a0mutations in patients with GD are localized within the region encoding the transforming growth factor-\u03b2 binding protein-like 5 (TB5) domain of this protein. Herein, we generated a knock-in mouse model,\u00a0Fbn1Y1698C<\/sup><\/em>\u00a0by introducing the p.Tyr1696Cys mutation from a patient with GD into the TB5 domain of murine Fbn1 to elucidate the specific role of this domain in endochondral ossification. We found that both\u00a0Fbn1<\/em>Y1698C<\/em>\/+<\/sup>\u00a0and\u00a0Fbn1Y1698C\/Y1698C<\/sup><\/em>\u00a0mice exhibited a reduced stature reminiscent of the human GD phenotype. The\u00a0Fbn1<\/em>\u00a0point mutation introduced in these mice affected the growth plate formation owing to abnormal chondrocyte differentiation such that mutant chondrocytes failed to establish a dense microfibrillar network composed of FBN1. This original\u00a0Fbn1<\/em>\u00a0mutant mouse model offers new insight into the pathogenic events underlying GD. Our findings suggest that the etiology of GD involves the dysregulation of the extracellular matrix composed of an abnormal FBN1 microfibril network impacting the differentiation of the chondrocytes.<\/p>\n

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