Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 109

Some ciliopathies in both humans and mice are associated with hyperphagia and obesity (e.g. Bardet–Biedl Syndrome, Alström Syndrome) [92]. Several mouse models recapitulate the human phenotypes and have proven useful in elucidating how sensory cilia influence appetite and the pathogenesis of obesity [93]. The sensory cilia on paraventricular nucleus neurons appear to control appetite by detecting signals from the arcuate nucleus. The tubby bipartite transcription factor (Tub^tub) mutant mouse, which develops progressive obesity and blindness, has defective trafficking of ciliary GPCRs in hypothalamic neurons [94]. Heterozygous mice hypomorphic for Rpgrip1l are leptin‐resistant, hyperphagic, and obese. The distribution and responses of leptin receptors in sensory cilia of hypothalamic neurons are abnormal in Rpgrip1l^tm1Urt mice [95]. Similarly, obese and hyperphagic Ankrd26^Gt(XK525)Byg mice have defective primary cilia in the hypothalamic paraventricular nucleus [92]. Again, since there are many different underlying mechanisms that can contribute to the development of obesity, other cilia‐related phenotypes must be present to suspect a ciliopathy.