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.
Experimental Neuromuscular Pathology Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.
Sci Rep. 2024 Aug 22;14(1):19479. doi: 10.1038/s41598-024-70529-w.
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.
芽蛋白家族（Spry1-4）的基因是受体酪氨酸激酶的反馈抑制剂，特别是 Ret 和 FGF 受体。因此，它们在胚胎形态发生中发挥着独特而重叠的作用，并被认为是成年生活中的肿瘤抑制因子。在小鼠中的遗传实验详细定义了这些基因在胚胎发育过程中的作用，然而，它们在成年小鼠中的功能尚不清楚。在这里，我们生成了成年期全身 Spry1/2/4 三重敲除小鼠。三重突变体小鼠的肿瘤发生率与野生型同窝仔鼠相当，直至一岁，表明芽蛋白缺失本身不足以引发肿瘤发生。另一方面，随着年龄的增长，三重敲除小鼠体重不会增加，内脏脂肪减少，血浆葡萄糖水平低于野生型同窝仔鼠，尽管它们的食物摄入量相似，运动功能略有下降。它们还表现出脱毛、眼睑炎症和轻度甲状腺功能亢进。最后，三重敲除小鼠出现磷酸尿和低磷血症，表明 FGF23 下游信号过度激活。总之，三重敲除小鼠表现出一系列内分泌异常，但肿瘤发生率没有增加。
