TY  - JOUR
A1  - Bultmann-Mellin, Insa
A1  - Conradi, Anne
A1  - Maul, Alexandra C.
A1  - Dinger, Katharina
A1  - Wempe, Frank
A1  - Wohl, Alexander P.
A1  - Imhof, Thomas
A1  - Wunderlich, F. Thomas
A1  - Bunck, Alexander C.
A1  - Nakamura, Tomoyuki
A1  - Koli, Katri
A1  - Bloch, Wilhelm
A1  - Ghanem, Alexander
A1  - Heinz, Andrea
A1  - Melchner, Harald von
A1  - Sengle, Gerhard
A1  - Sterner-Kock, Anja
T1  - Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms
T2  - Disease models & mechanisms
N2  - Recent studies have 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 human gene involved in ARCL1C has been 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, and showed that it has distinct tissue expression patterns and specific molecular functions. We identified fibulin-4 as a previously unknown interaction partner of both Ltbp-4 isoforms and demonstrated that at least Ltbp-4L expression is essential for incorporation of fibulin-4 into the extracellular matrix (ECM). Overall, our results contribute to the current understanding of elastogenesis and provide an animal model of ARCL1C.
KW  - Latent transforming growth factor β-binding protein 4
KW  - Ltbp-4
KW  - Ltbp-4L
KW  - Ltbp-4S
KW  - Autosomal recessive cutis laxa type 1C
KW  - Elastogenesis
KW  - Extracellular matrix
KW  - ECM
KW  - Fibulin-4
KW  - Fibulin-5
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37355
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373550
SN  - 1754-8411
SN  - 1754-8403
N1  - Copyright © 2015. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
VL  - 8
IS  - 4
SP  - 403
EP  - 415
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -