The present observations suggest that the two receptors cubilin and megalin are both involved in the endocytic uptake of albumin in renal proximal tubule cells.

Abstract. Mice are prime targets of experimental gene modification and have become object of an increasing number of biologic studies in renal physiology, development, and molecular biology. Phenotypic changes in response to gene modification require detailed information on normal structure. However, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from each kidney from the surface to the inner stripe of the outer zone of medulla. All tubules were reconstructed in 3D and visualized by interactive computer graphics. A quantitative ultrastructural analysis of the mouse proximal tubule at every 300 to 400 m was performed. The 3D representation revealed a distinct organization of the mouse proximal tubule, each occupying a separate domain within the cortex. Superficial proximal tubules have long straight parts converging into clusters within the medullary rays. Tubules originating deeper within the cortex become longer and increasingly tortuous. In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice. In conclusion, significant new information on the 3D organization of the murine proximal tubule has been obtained. Quantitative, ultrastructural analyses of mouse proximal tubules reveal substantial differences compared with other species.Over the last decade, the mouse kidney has become the target for an increasing number of functional and morphologic studies. Gene-deleted and transgenic mice have become important tools for the study of a variety of physiologic and pathophysiologic parameters. To be able to recognize structural changes in genetically modified kidneys, it is therefore pertinent to obtain information on the normal architecture of mouse nephrons.In the literature, structural and functional parameters of the mouse proximal tubule are often correlated to the segmentation well described in other species. The rat proximal tubule segmentation has been intensively studied at the ultrastructural level, subdividing it into three segments (1); studies on mouse proximal tubules often refer to this segmentation. Although the ultrastructure of mouse proximal tubules has been described to some extent (see reference 2), detailed information, including the verification of any segmental, structural variation is required.Only little information on the three-dimensional organization of the mouse renal proximal tubule is available, limited mainly to the identification of a convoluted and a straight part, the latter being located in the medullary rays. A more detailed description of the tubular organization may be of interest ...

BackgroundMcCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients.MethodClinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained.ResultsWe reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications.ConclusionMcCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.