Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice.

Animals Mice, Knockout Mice Membrane Proteins / genetics Phosphoproteins / genetics Fibroblast Growth Factor-23 Adaptor Proteins, Signal Transducing / genetics Intracellular Signaling Peptides and Proteins / genetics Female Male Endocrine System Diseases / genetics Nerve Tissue Proteins Protein Serine-Threonine Kinases

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
22 08 2024
Historique:
received: 29 05 2024
accepted: 19 08 2024
medline: 23 8 2024
pubmed: 23 8 2024
entrez: 22 8 2024
Statut: epublish

Résumé

Genes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinases, especially of Ret and the FGF receptors. As such, they play distinct and overlapping roles in embryo morphogenesis and are considered to be tumor suppressors in adult life. Genetic experiments in mice have defined in great detail the role of these genes during embryonic development, however their function in adult mice is less clearly established. Here we generate adult-onset, whole body Spry1/2/4 triple knockout mice. Tumor incidence in triple mutant mice is comparable to that of wild type littermates of up to one year of age, indicating that Sprouty loss per se is not sufficient to initiate tumorigenesis. On the other hand, triple knockout mice do not gain weight as they age, show less visceral fat, and have lower plasma glucose levels than wild type littermates, despite showing similar food intake and slightly reduced motor function. They also show alopecia, eyelid inflammation, and mild hyperthyroidism. Finally, triple knockout mice present phosphaturia and hypophosphatemia, suggesting exacerbated signaling downstream of FGF23. In conclusion, triple knockout mice develop a series of endocrine abnormalities but do not show increased tumor incidence.

Identifiants

DOI: 10.1038/s41598-024-70529-w PMID: 39174793
pubmed: 39174793
doi: 10.1038/s41598-024-70529-w
pii: 10.1038/s41598-024-70529-w
doi:

Substances chimiques

Spry1 protein, mouse 0
Membrane Proteins 0
Spry4 protein, mouse 0
Spry2 protein, mouse EC 2.7.11.1
Phosphoproteins 0
Fibroblast Growth Factor-23 7Q7P4S7RRE
Adaptor Proteins, Signal Transducing 0
Intracellular Signaling Peptides and Proteins 0
Fgf23 protein, mouse 0
Nerve Tissue Proteins 0
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

19479

Subventions

Organisme : MICIU/AEI/10.13039/501100011033
ID : PID2020-114947GB-I00

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Gisela Altés (G)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Anna Olomí (A)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Aida Perramon-Güell (A)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Sara Hernández (S)

Experimental Neuromuscular Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Anna Casanovas (A)

Experimental Neuromuscular Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Aurora Pérez (A)

Vascular and Renal Translational Research Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Juan Miguel Díaz-Tocados (JM)

Vascular and Renal Translational Research Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

José Manuel Valdivielso (JM)

Vascular and Renal Translational Research Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Cristina Megino (C)

Oncologic Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Raúl Navaridas (R)

Oncologic Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Xavier Matias-Guiu (X)

Oncologic Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.
Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain.

Ophir D Klein (OD)

Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA.
Department of Pediatrics, Cedars-Sinai Guerin Children's, Los Angeles, CA, USA.

Joaquim Egea (J)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Xavi Dolcet (X)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Andrée Yeramian (A)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain.

Mario Encinas (M)

Developmental and Oncogenic Signaling Group, Edifici Biomedicina I, Lab 2.8, Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, 25198, Lleida, Spain. mario.encinas@mex.udl.cat.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Facteur-23 de croissance des fibroblastes › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Maladies endocriniennes › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Multiple endocrine defects in adult-onset...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Multiple endocrine defects in adult-onset...