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Updated: Jul 28, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice
Gisela Altés1, Anna Olomí1, Aida Perramon-Güell1
1Developmental 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.
Abstract:
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.
Insights
Sprouty gene loss in adult mice does not increase tumor incidence but causes metabolic and endocrine issues, including weight loss and hyperthyroidism. These findings highlight Sprouty proteins' roles beyond embryonic development.
Area of Science:
- Molecular Biology
- Endocrinology
- Developmental Biology
Background:
- Sprouty genes (Spry1-4) are key feedback inhibitors of receptor tyrosine kinases, crucial for embryonic development.
- Their roles in adult physiology and tumor suppression are less understood compared to their embryonic functions.
Purpose of the Study:
- To investigate the physiological and tumor-related consequences of adult-onset, whole-body Sprouty gene deficiency.
- To determine if Sprouty loss is sufficient for tumorigenesis in adult mice.
Main Methods:
- Generation of adult-onset, whole-body Spry1/2/4 triple knockout mice.
- Comparative analysis of tumor incidence, body weight, metabolism, and endocrine function between knockout and wild-type mice.
Main Results:
- Triple knockout mice showed no increased tumor incidence up to one year of age.
- Significant metabolic changes observed: reduced weight gain, less visceral fat, lower plasma glucose, and phosphaturia with hypophosphatemia.
- Endocrine abnormalities included alopecia, eyelid inflammation, and mild hyperthyroidism, suggesting dysregulated FGF23 signaling.
Conclusions:
- Sprouty gene loss alone is insufficient to initiate tumorigenesis in adult mice.
- Complete loss of Sprouty function leads to a spectrum of endocrine and metabolic dysregulations in adult mice.
- These findings reveal critical roles for Sprouty genes in maintaining adult physiological homeostasis.
