Congenital genetic murine (ch) hydrocephalus. A structural model of cellular dysplasia and disorganization with the molecular locus of deficient proteoglycan synthesis.

The recessively inherited ch hydrocephalic mouse has been sporadically investigated over the past 40 years as a genetic murine model for congenital hydrocephalus. Since central nervous system anomalies are commonly associated with congenital anomalies in the musculoskeletal and urogenital systems, and since congenital hydrocephalus is also associated with other developmental abnormalities, an understanding of the pathophysiology at the cellular and molecular levels of the genetic defects of this hydrocephalic murine model has application to related human disorders associated with hydrocephalus. A unifying hypothesis is presented that can interrelate the multisystem developmental abnormalities. While the basic cellular defect is a failure of mesenchymal differentiation, the molecular locus is a synthetic defect in the production of the chondroitin sulfate proteoglycan. The primary end results of defective proteoglycan synthesis at a multiorgan-multisystem level includes chondrodysplasia, renal dysplasia, failure of endochondral ossification and gonadal development, and defective development of the adrenal medulla and the sympathetic ganglia. The development of the severe, communicating, congenital hydrocephalus in the ch mouse may be either a primary or secondary manifestation of the mesenchymal maldifferentiation.