# Fibrillin-1 G234D mutation in the hybrid1 domain causes tight skin associated with dysregulated elastogenesis and increased collagen cross-linking in mice https://mdr.nims.go.jp/datasets/faf7ab8a-467e-4600-bc26-f1010d3bb2a4 ## File - [1-s2.0-S0945053X24001422-main.pdf](https://mdr.nims.go.jp/filesets/9a732c62-b0e0-424e-8afd-ed56d7db500e/download) ([Detail](https://mdr.nims.go.jp/filesets/9a732c62-b0e0-424e-8afd-ed56d7db500e.md)) ## Id faf7ab8a-467e-4600-bc26-f1010d3bb2a4 ## Local identifier ## Visibility open_to_public ## State published ## Created at 2026-09-17T06:16:04.617409Z ## Updated at 2026-09-17T06:51:53.303377Z ## Published at 2026-09-17T09:31:22.888539Z ## Doi ## First published url https://doi.org/10.1016/j.matbio.2024.11.006 ## Date published 2024-11-28 ## Recorded date published 2025-2 ## Resource type journal_article ## Manuscript type vor ## Collection ## Title - title: Fibrillin-1 G234D mutation in the hybrid1 domain causes tight skin associated with dysregulated elastogenesis and increased collagen cross-linking in mice title_type: original lang: en ## Description - description: Fibrillin-1, an extracellular matrix (ECM) protein encoded by the FBN1 gene, serves as a microfibril scaffold crucial for elastic fiber formation and homeostasis in pliable tissue such as the skin. Aside from causing Marfan syndrome, some mutations in FBN1 result in scleroderma, marked by hardened and thicker skin which limits joint mobility. Here, we describe a tight skin phenotype in the Fbn1G234D/G234D mice carrying a corresponding variant of FBN1 in the hybrid1 domain that was identified in a patient with familial aortic dissection. Unlike scleroderma, skin thickness and collagen fiber abundance do not change in the Fbn1G234D/G234D mutant skin. Instead, increased collagen cross-links were observed. In addition, short elastic fibers were sparsely located underneath the panniculus muscle layer, and an abundance of thin, aberrant elastic fibers was increased within the subcutaneous fascia, which may have tightened skin attachment to the underlying skeletal muscle. Structurally, Fbn1G234D/G234D microfibrils have a disrupted shoulder region that shares similarities with hybrid1 deletion mutant microfibrils. We then demonstrate the consequence of fibrillin-1 G234D mutation on dermal fibroblast functions. Mutant primary fibroblasts produce fewer elastic fibers, exhibit slower migration and increased cell stiffness. Moreover, secretome from mutant fibroblasts are marked by enhanced secretion of ECM, ECM-modifying enzymes, proteoglycans and cytokines, which are pro-tissue repair/fibrogenic. The transcriptome of mutant fibroblasts displays an increased expression of myogenic developmental and immune-related genes. Our study proposes that imbalanced ECM homeostasis due to a fibrillin-1 G234D mutation impacts fibroblast properties with potential ramifications on skin function. description_type: abstract lang: en ## Creator - name: ASM Sakhawat Hossain role: author organization: University of Tsukuba, Japan department: Graduate School of Comprehensive Human Sciences - name: Maria Thea Rane Dela Cruz Clarin role: author - name: Kenichi Kimura role: author - name: George Biggin role: author - name: Yuki Taga role: author - name: Koichiro Uto role: author - name: Ayana Yamagishi role: author - name: Eri Motoyama role: author - name: Narenmandula role: author - name: Kazunori Mizuno role: author - name: Chikashi Nakamura role: author - name: Keiichi Asano role: author - name: Sumio Ohtsuki role: author - name: Tomoyuki Nakamura role: author - name: Sachiko Kanki role: author - name: Clair Baldock role: author - name: Erna Raja role: author - name: Hiromi Yanagisawa role: author ## Contact agent ## Publisher organization: Elsevier BV ## Managing organization ## Keyword - subject: Fibrillin-1 schema: not_defined - subject: Tight skin schema: not_defined - subject: Fibroblasts schema: not_defined - subject: Extracellular matrix schema: not_defined - subject: Collagen cross-linking; Elastic fibers; Fascia schema: not_defined - subject: Elastic fibers schema: not_defined - subject: Fascia schema: not_defined ## Rights - identifier: https://creativecommons.org/licenses/by-nc-nd/4.0/ ## Other identifier(s) ## Data origin - data_origin_type: other ## Embargo ## Journal - title: Matrix Biology issn: '0945053X' volume: '135' start_page: 24 end_page: 38 ## Conference ## Related item ## Funding - identifier: 23ek0109553h003 funder_name: Japan Agency for Medical Research and Development - identifier: 23ek0210183h0001 funder_name: Japan Agency for Medical Research and Development - identifier: SCR_021147 funder_name: University of Tsukuba - funder_name: The Marfan Foundation - identifier: BB/T008725/1 funder_name: Biotechnology and Biological Sciences Research Council - funder_name: Ministry of Education, Culture, Sports, Science and Technology - identifier: 23K07737 funder_name: Japan Society for the Promotion of Science - identifier: 23H04937 funder_name: Japan Society for the Promotion of Science - identifier: 21KK0151 funder_name: Japan Society for the Promotion of Science - identifier: 23H00431 funder_name: Japan Society for the Promotion of Science - identifier: 23ama121018 funder_name: Japan Society for the Promotion of Science - identifier: '2022' funder_name: Japan Society for the Promotion of Science ## Instrument ## Instrument operator ## Instrument managing organization ## Measurement method ## Specimen ## Chemical composition ## Structure for specimen ## Structural feature for specimen ## Specific property for specimen ## Process for specimen treatment ## Computational method ## Energy level/transition state ## Software ## Custom property ## Fileset - id: 9a732c62-b0e0-424e-8afd-ed56d7db500e filename: 1-s2.0-S0945053X24001422-main.pdf content_type: application/pdf size: 17890787 md5: e5c10149712b510d57b06412bca73e06 ## Thumbnail fileset_id: 9a732c62-b0e0-424e-8afd-ed56d7db500e filename: 1-s2.0-S0945053X24001422-main.pdf