Rescue of Human ABCC6 Mutants in Mouse Liver
Author Information
Author(s): Le Saux Olivier, Fülöp Krisztina, Yamaguchi Yukiko, Iliás Attila, Szabó Zalán, Brampton Christopher N., Pomozi Viola, Huszár Krisztina, Arányi Tamás, Váradi András
Primary Institution: John A. Burns School of Medicine, University of Hawaii
Hypothesis
The study aims to identify mutants of the ABCC6 protein with preserved transport activity but impaired intracellular targeting.
Conclusion
The study demonstrates that certain ABCC6 mutants can have their intracellular trafficking restored using the drug 4-phenylbutyrate.
Supporting Evidence
- The study identified five missense mutations in the ABCC6 gene.
- Two mutants, R1138Q and R1314W, retained significant transport activity.
- 4-phenylbutyrate treatment improved the localization of the R1314W mutant in mouse liver.
Takeaway
Some faulty proteins in the liver can be fixed with a special medicine, helping them work better.
Methodology
The study involved expressing ABCC6 mutants in mouse liver using hydrodynamic tail vein injections and assessing their localization and transport activity.
Limitations
The study primarily focused on a limited number of mutations and their effects in a mouse model, which may not fully represent human conditions.
Digital Object Identifier (DOI)
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