Laminin N-terminus α31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model



Sugden, Conor J ORCID: 0000-0002-9543-1676, Iorio, Valentina, Troughton, Lee D, Liu, Ke, Morais, Mychel RPT, Lennon, Rachel, Bou-Gharios, George and Hamill, Kevin J ORCID: 0000-0002-7852-1944
(2022) Laminin N-terminus α31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model. FASEB JOURNAL, 36 (7). e22318-.

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Abstract

Laminins (LMs) are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non-laminin but netrin-like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing. In vitro functional studies have shown that LaNt α31 can influence numerous aspects of epithelial cell behavior via modifying matrix organization, suggesting a new model of laminin auto-regulation. However, the function of this protein has not been established in vivo. Here, a mouse transgenic line was generated using the ubiquitin C promoter to drive inducible expression of LaNt α31. When expression was induced at embryonic day 15.5, LaNt α31 transgenic animals were not viable at birth, exhibiting localized regions of erythema. Histologically, the most striking defect was widespread evidence of extravascular bleeding across multiple tissues. Additionally, LaNt α31 transgene expressing animals exhibited kidney epithelial detachment, tubular dilation, disruption of the epidermal basal cell layer and of the hair follicle outer root sheath, and ~50% reduction of cell numbers in the liver, associated with depletion of hematopoietic erythrocytic foci. These findings provide the first in vivo evidence that LaNt α31 can influence tissue morphogenesis.

Item Type: Article
Uncontrolled Keywords: basement membrane, development, laminin, netrin
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Jun 2022 13:58
Last Modified: 18 Oct 2023 02:41
DOI: 10.1096/fj.202002588RRR
Open Access URL: https://faseb.onlinelibrary.wiley.com/doi/full/10....
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3156376