In:
Disease Models & Mechanisms, The Company of Biologists
Abstract:
Recent studies revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the mechanisms underlying the disease were discovered based on similar elastic fiber abnormalities exhibited by mice lacking the short Ltbp-4 isoform (Ltbp4S-/-), the murine phenotype does not replicate ARCL1C. We therefore inactivated both Ltbp-4 isoforms in the mouse germline to model ARCL1C. Comparative analysis of Ltbp4S-/- and Ltbp4 null (Ltbp4-/-) mice identified Ltbp-4L as an important factor for elastogenesis and postnatal survival with distinct tissue expression patterns and specific molecular functions. We identified fibulin-4 as a novel interaction partner of both Ltbp-4 isoforms and demonstrated that at least Ltbp-4L expression is essential for ECM incorporation of fibulin-4. Overall, our results contribute to the current understanding of elastogenesis and provide of an animal model of ARCL1C.
Type of Medium:
Online Resource
ISSN:
1754-8411
,
1754-8403
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2015
detail.hit.zdb_id:
2451104-3
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