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World J Gastroenterol. May 21, 2026; 32(19): 113022
Published online May 21, 2026. doi: 10.3748/wjg.v32.i19.113022
Published online May 21, 2026. doi: 10.3748/wjg.v32.i19.113022
Serca2 deletion in the mouse adult Bmi1+ compartment induces a lethal phenotype involving a severe gastric dysfunction
Diego Herrero, Antonio Docavo, María Salvador, Marina Higuera, Miguel A García-Brenes, Guillermo Albericio, Alejandra Cordero, Jesús M Salvador, Antonio Bernad, Department of Immunology and Oncology, National Center for Biotechnology (CNB.CSIC), Madrid 28049, Spain
Alfonso Cortés, Center of Cytometry and Fluorescence Microscopy, Complutense University, Madrid 28040, Spain
Javier García-Ceca, Sara Montero-Herradón, Agustín G Zapata, Health Research Institute, Hospital 12 de Octubre (imas12), Madrid 28041, Spain
Javier García-Ceca, Sara Montero-Herradón, Agustín G Zapata, Department of Cell Biology and Histology, Faculty of Biological Sciences, Complutense University of Madrid, Madrid 28040, Spain
Rosa M Carmona, Department of Cardiovascular, National Center for Cardiovascular Research, Madrid 28049, Spain
Antonio de Molina, Department of CNIC Histopathology, National Center for Cardiovascular Research, Madrid 28029, Spain
Carmen Mora, Department of Business, MedSir Org, Madrid 28049, Spain
Co-first authors: Diego Herrero and Antonio Docavo.
Co-corresponding authors: Agustín G Zapata and Antonio Bernad.
Author contributions: Herrero D and Docavo A performed the main block of experiments, collected data and performed data analysis; Salvador M, Higuera M, García-Brenes MA, Cortés A, García-Ceca J, Montero-Herradón S and Roche E collaborated in specific aspects of the research program, collected data and performed data analysis; Cordero A and Carmona RM has been the main responsible for the coordination of the different mouse colonies and genotyping; Albericio G and Higuera M have supervised different experimental aspects of the project; Bernad A conceived the project, designed the global strategy and supervised research; Salvador JM and Mora C have co-coordinated the lymphohematopoietic analysis of the KO mice; Zapata AG, García-Ceca J, Montero-Herradón S have been the main responsible of the dissection of the thymic phenotype; Bernad A wrote and edited the manuscript with the main collaboration of Higuera M and Zapata AG; Herrero D, Docavo A, Salvador M, Higuera M, Cortés A, García-Ceca J, Montero-Herradón S, García-Brenes MA, Albericio G, Cordero A, Carmona RM, de Molina A, Salvador JM, Mora C, Zapata AG, Bernad A read and approved the final manuscript.
Supported by the Spanish Ministry of Science and Innovation, AEI/FEDER, UE, No. RTI2018-097604-B-I00; The Instituto de Salud Carlos III, Cell Therapy Network, TERCEL, No. RD16/0011/0037; The Spanish Ministry of Science, Innovation and Universities, No. RTI2018-093938-B-I00; The Carlos III Health Institute, Cell Therapy Network, TERCEL, No. RD16/0011/0002; and The program has been funded by the Regional Government of Madrid Program, Avancell, No. B2017/BMD-3692.
Institutional review board statement: This study did not involve human participants, consequently, institutional review board statement and approval, and informed consent procedures were not applicable. The project (RTI2018-097604-B-I00) has been evaluated (Ref. REGAGE25e00055149413) by the specific panels for Biomedicine of the Spanish Ministry of Science and Innovation and the Cell Therapy of the National Healthy Institute, Carlos III (RD16/0011/0037) and the Ethical CSIC Committee. These evaluations involved the argumentation on the use of specific human cells and a detailed justification of the animal work.
Institutional animal care and use committee statement: Animal studies were approved (Ref. 23002) by the Ethics Committee of the National Center for Biotechnology (CEEA-CNB).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Authors be willing to distribute any materials and protocols used in the published experiments to qualified researchers for their own use. These must be made available with minimal restrictions and in a timely manner. Specific data sets must be made freely available to readers from the date of publication upon request.
Corresponding author: Antonio Bernad, MD, Doctor, Department of Immunology and Oncology, National Center for Biotechnology (CNB.CSIC), C/Darwin 3 Universidad Autónoma de Madrid Campus de Cantoblanco, Madrid 28049, Spain. abernad@cnb.csic.es
Received: August 13, 2025
Revised: October 28, 2025
Accepted: February 25, 2026
Published online: May 21, 2026
Processing time: 278 Days and 23 Hours
Revised: October 28, 2025
Accepted: February 25, 2026
Published online: May 21, 2026
Processing time: 278 Days and 23 Hours
Core Tip
Core Tip: Although cytoplasmic [calcium ions (Ca2+)] plays an important role in regulating several critical cellular processes, low information is available regarding intestinal stem cells (ISC). Recent seminal results, obtained in Drosophila melanogaster, have demonstrated that the reduction of Ca2+ in ISC increases their proliferation rate; downregulation of Serca is one of the main genes involved. Based on these relevant results, and taking advantage of a dedicated mouse models, we have demonstrated that the deletion of Serca2 in the intestinal Bmi1+ populations provokes, unexpectedly, a lethal phenotype, associated with a severe malnutrition. Furthermore, because this promotes ISC proliferation rate a moderate reduction of Serca2 activity could be involved in some neoplasic conditions.