ABSTRACT
Coil-coiled domain containing 85c (Ccdc85c) is a causative gene for congenital hydrocephalus and subcortical heterotopia with frequent brain hemorrhage. We established Ccdc85c knockout (KO) rats and investigated the roles of CCDC85C and intermediate filament protein expression, including nestin, vimentin, GFAP, and cytokeratin AE1/AE3 during the lateral ventricle development in KO rats to evaluate the role of this gene. We found altered and ectopic expression of nestin and vimentin positive cells in the wall of the dorso-lateral ventricle in the KO rats during development from the age of postnatal day (P) 6, whereas both protein expression became faint in the wild-type rats. In the KO rats, there was a loss of cytokeratin expression on the surface of the dorso-lateral ventricle with ectopic expression and maldevelopment of ependymal cells. Our data also revealed disturbed GFAP expression at postnatal ages. These findings indicate that lack of CCDC85C disrupts the proper expression of intermediate filament proteins (nestin, vimentin, GFAP, and cytokeratin), and CCDC85C is necessary for normal neurogenesis, gliogenesis, and ependymogenesis.
Subject(s)
Hydrocephalus , Rats , Animals , Nestin/genetics , Vimentin/genetics , Vimentin/metabolism , Hydrocephalus/genetics , Hydrocephalus/metabolism , Neurogenesis/genetics , KeratinsABSTRACT
Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for genetic hydrocephalus and subcortical heterotopia with frequent brain hemorrhage. In the present study, we examined the expression pattern of CCDC85C protein and intermediate filament proteins, such as nestin, vimentin, GFAP, and cytokeratin AE1/AE3, during lateral ventricle development in rats. CCDC85C was expressed in the neuroepithelial cells of the dorsal lateral ventricle wall, diminishing with development and almost disappearing at postnatal day 20. By immunoelectron microscopy, CCDC85C was localized in the cell-cell junction and apical membrane. The expression of nestin and vimentin was decreased in the wall of the lateral ventricle in manner similar to CCDC85C, but GFAP expression started immediately after birth and became stronger with age. Moreover, cytokeratin expression was found at postnatal day 13 and increased at postnatal day 20 in conjunction with the disappearance of CCDC85C expression. Taken together, CCDC85C is expressed in the cell-cell junctions lining the wall of the lateral ventricle and plays a role in neural development with other intermediate filaments in the embryonic and postnatal periods. Our chronological study will help to relate CCDC85C protein with intermediate filaments to elucidate the detailed role of CCDC85C protein during neurogenesis.
Subject(s)
Hydrocephalus , Lateral Ventricles , Animals , Hydrocephalus/genetics , Nerve Tissue Proteins/genetics , Neurogenesis , RatsABSTRACT
We report a spontaneous case of nephroblastoma in a 26-week-old female Slc:CD(SD) rat. Macroscopically, there was a yellow mass in the left kidney that included another small yellowish-white mass. Histologically, the mass was located mainly in the cortex of the kidney. The tumor showed two distinct morphologies corresponding to the macroscopic findings: a blastemal cell dominant area (blastemal area) with primitive glomeruli and immature tubules and a columnar epithelial tubule dominant area with blastemal cell cuffing on (epithelial area). The epithelial area was located inside the blastemal area and the two morphologies were characterized by the lack of a transition region. Nephroblastoma is known to be biphasic or triphasic and showing transitional features. To our knowledge, there is no report of such nephroblastoma comprising two histologically distinct areas without transition. Therefore, the two distinct morphologies of this case with no transitional characteristic is a rare feature in nephroblastoma.
ABSTRACT
Spontaneous hhy mice show hydrocephalus and subcortical heterotopia, and a mutation in the Ccdc85c gene has been identified. To contribute to the comparison of the role of Ccdc85c in different species, we established a Ccdc85c KO rat and investigated its pathological phenotypes. Ccdc85c KO rats were produced by genomic engineering using transcription activator-like effector nuclease (TALEN). The KO rats had an approximately 350-bp deletion in Ccdc85c and lacked CCDC85C protein expression. The KO rats showed non-obstructive hydrocephalus, subcortical heterotopia, and intracranial hemorrhage. The KO rats had many pathological characteristics similar to those in hhy mice. These results indicate that CCDC85C plays an important role in cerebral development in rats, and the function of CCDC85C in the cerebrum are similar in rats and mice.
Subject(s)
Hydrocephalus/pathology , Nerve Tissue Proteins/genetics , Animals , Disease Models, Animal , Hydrocephalus/genetics , Mutation , Nerve Tissue Proteins/metabolism , Phenotype , RatsABSTRACT
The term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. It is rare in cynomolgus macaques (Macaca fascicularis). Here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. Macroscopically, the interventricular septum (IVS) and the left ventricular (LV) and right ventricular (RV) walls of the heart were thickened. Histologically, cardiomyocytes showed hypertrophy and disarray with interstitial fibrosis, and some myocytes showed karyomegaly and vacuoles. On the basis of these morphological characteristics, the present case was diagnosed as hypertrophic cardiomyopathy. Immunohistochemically, the cardiomyocytes in the affected regions were positive for the autophagic markers LC3 and p62/SQSTM1 (p62). The accumulation of autophagosomes in hypertrophied cardiomyocytes was demonstrated. The mechanism of accumulation of autophagosomes seems to be a secondary effect due to stress. To our knowledge, this is the first report of spontaneous hypertrophic cardiomyopathy in a cynomolgus macaque.
