Tgfbi/Bigh3 silencing activates ERK in mouse retina
Nathalie Allaman-Pillet1, Anne Oberson1, Mauro Bustamante1
1Institut de Recherche en Ophtalmologie, Sion, Switzerland.
Abstract:
BIGH3 is a secreted protein, part of the extracellular matrix where it interacts with collagen and integrins on the cell surface. BIGH3 can play opposing roles in cancer, acting as either tumor suppressor or promoter, and its mutations lead to different forms of corneal dystrophy. Although many studies have been carried out, little is known about the physiological role of BIGH3. Using the cre-loxP system, we generated a mouse model with disruption of the Bigh3 genomic locus. Bigh3 silencing did not result in any apparent phenotype modifications, the mice remained viable and fertile. We were able to determine the presence of BIGH3 in the retinal pigment epithelium (RPE). In the absence of BIGH3, a transient decrease in the apoptotic process involved in retina maturation was observed, leading to a transient increase in the INL thickness at P15. This phenomenon was accompanied by an increased activity of the pro-survival ERK pathway.
Insights
The secreted protein BIGH3 is found in the retinal pigment epithelium (RPE). Its absence causes transient changes in retina maturation and apoptosis, affecting the inner nuclear layer (INL) and ERK pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Developmental Biology
Background:
- BIGH3 is an extracellular matrix protein interacting with collagen and cell surface integrins.
- BIGH3 has dual roles in cancer (suppressor or promoter) and is implicated in corneal dystrophies.
- The precise physiological role of BIGH3 remains largely unknown.
Purpose of the Study:
- To investigate the physiological role of BIGH3 using a genetically modified mouse model.
- To determine the impact of BIGH3 disruption on mouse development and specific tissues.
Main Methods:
- Generation of a Bigh3 genomic locus disruption using the cre-loxP system in mice.
- Phenotypic analysis of Bigh3-silenced mice for viability, fertility, and developmental modifications.
- Localization of BIGH3 within the retinal pigment epithelium (RPE).
Main Results:
- Bigh3 silencing did not cause major phenotypic alterations; mice were viable and fertile.
- BIGH3 was detected in the retinal pigment epithelium (RPE).
- Absence of BIGH3 led to a transient decrease in apoptosis during retina maturation, increasing inner nuclear layer (INL) thickness at P15.
- This was associated with enhanced activity of the pro-survival ERK pathway.
Conclusions:
- BIGH3 plays a role in regulating apoptosis during retinal development.
- The study identifies BIGH3's presence in the RPE and its influence on retinal maturation processes.
- BIGH3's function in retina development involves modulation of the ERK pro-survival pathway.
