Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2 †
Abstract
1. Introduction
2. Results
2.1. Three-Dimensional Structure Analysis Predicts a Folding Defect of the Abcb11R1128C Variant
2.2. Effect of 4-Phenylbutyrate, Glycerol Phenylbutyrate and Phenylacetate on the Localization and the Function of the Abcb11R1128C Variant
2.3. Identification of 4-Phenylbutyrate-Analogs or Homologs
2.4. Effect of the 4-Phenylbutyrate-Analogs or Homologs on the Localization and the Function of the Abcb11R1128C Variant
2.5. Effect of UDCA and of Other Non-4-PB Related Chemical Correctors on the Localization and the Function of the Abcb11R1128C Variant
3. Discussion
4. Materials and Methods
4.1. Chemistry Materials
4.2. Chemical Synthetic Procedures
4.2.1. The Methyl 3-Hydroxy-2-methyl-4-phenyl Butyric Ester (MHMPB)
4.2.2. The 3-Hydroxy-2-methyl-4-phenylbutyrate (HMPB)
4.2.3. General Procedure for Methyl (E)-2-Methyl-4-phenylbut-3-enoate (MMPB-3E) and Methyl (E)-2-Methyl-4-phenylbut-2-enoate (MMPB-2E)
4.3. Three-Dimensional (3D) Structure Analysis
4.4. DNA Constructs and Mutagenesis
4.5. Transfection, Treatment and Quantification of Cells with Abcb11 Localized at the Canalicular Membrane
4.6. Generation of MDCK Clones Stably Expressing Abcb11 and Ntcp
4.7. Taurocholate Transport Assay
4.8. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BA | Bile acid |
BSEP | Bile salt export pump |
CF | Cystic fibrosis |
ER | Endoplasmic reticulum |
GPB | Glycerol phenylbutyrate |
HMPB | 3-Hydroxy-2-methyl-4-phenylbutyrate |
[3H]-TC | 3H-Taurocholate |
MHMPB | Methyl 3-hydroxy-2-methyl-4-phenyl butyric ester |
MMPB-2E | Methyl (E)-2-methyl-4-phenylbut-2-enoic ester |
MMPB-3E | Methyl (E)-2-methyl-4-phenylbut-3-enoic ester |
OTNC | 4-Oxo-1,2,3,4-tetrahydro-naphthalene-2-carboxylate |
PA | Phenylacetate |
4-PB | 4-phenylbutyrate |
PFIC2 | Progressive Familial Intrahepatic Cholestasis Type 2 |
SAHA | Suberoylanilide hydroxamic acid |
UDCA | Ursodeoxycholic acid |
wt | Wild type |
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Lapalus, M.; Mareux, E.; Amzal, R.; Drège, E.; Riahi, Y.; Petit, S.; Banet, M.; Falguières, T.; Callebaut, I.; Figadère, B.; et al. Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2. Int. J. Mol. Sci. 2025, 26, 5232. https://doi.org/10.3390/ijms26115232
Lapalus M, Mareux E, Amzal R, Drège E, Riahi Y, Petit S, Banet M, Falguières T, Callebaut I, Figadère B, et al. Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2. International Journal of Molecular Sciences. 2025; 26(11):5232. https://doi.org/10.3390/ijms26115232
Chicago/Turabian StyleLapalus, Martine, Elodie Mareux, Rachida Amzal, Emmanuelle Drège, Yosra Riahi, Sylvain Petit, Manon Banet, Thomas Falguières, Isabelle Callebaut, Bruno Figadère, and et al. 2025. "Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2" International Journal of Molecular Sciences 26, no. 11: 5232. https://doi.org/10.3390/ijms26115232
APA StyleLapalus, M., Mareux, E., Amzal, R., Drège, E., Riahi, Y., Petit, S., Banet, M., Falguières, T., Callebaut, I., Figadère, B., Joseph, D., Gonzales, E., & Jacquemin, E. (2025). Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2. International Journal of Molecular Sciences, 26(11), 5232. https://doi.org/10.3390/ijms26115232