Abstract
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 afailure ofmesenchymal differentiation, the molecular locus is asynthetic 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Asseher AW, Moffat DB, Sanders E (1982) Nephrology illustrated. Saunders, Philadelphia, pp 1.1–2.26
Breen M, Richardson R, Bondareff W, Weinstein HG (1973) Acidic glycosaminoglycans in developing sterno-costal cartilage of the hydrocephalic (ch+/ch+) mouse. Biochim Biophys Acta 304:828–836
Breen M, Weinstein HG, Anderson M, Veis A (1970) Micro-analysis and characterization of acidic glycosaminoglycans in human tissues. Anal Biochem 35:146–159
Chen JM (1952) Studies on the morphogenesis of the mouse sternum. I. Normal embryonic development. II. Experiments on the origin of the sternum and its capacity for self-differentiation. In Vitro J Anat 86:373–401
Frantantoni JC, Hall CW, Neufeld EF (1968) The defect in Hurler's and Hunter's syndromes. I. Proc Natl Acad Sci USA 60:699–706
Frantantoni JC, Hall CW, Neufeld EF (1969) The defect in Hurler's and Hunter's syndromes. II. Deficiency of specific factors involved in mucopolysaccharide degradation. Proc Natl Acad Sci USA 64:360–366
Gladstone RJ, Wakeley CPG (1932) The morphology of the sternum and its relation to the ribs. J Anat 66:509–564
Glenister TW (1976) An embryological view of cartilage. J Anat 122:323–330
Green MC (1970) The developmental effects of congenital hydrocephalus (ch) in the mouse. Dev Biol 23:585–608
Grüneberg H (1943) Congenital hydrocephalus in the mouse: a case of spurious pleiotropism. J Genet 45:1–21
GrÜneberg H (1953) Genetical studies on the skeleton of the mouse. VII. Congenital hydrocephalus. J Genet 51:327–358
Levitt R, Dorfman A (1974) Concepts and mechanisms of cartilage differentiation. Curr Top Dev Biol 8:103–149
Luna LG (1968) Manual of histologic staining method of the US Armed Forces Institute of Pathology, 3rd edn. McGraw-Hill, New York
Matukas VJ, Panner BJ, Orbison JL (1967) Studies on ultrastructural identification and distribution of protein-polysac-charide in cartilage matrix. J Cell Biol 32:365–378
O'Brien JS (1972) Sanfilippo syndrome: profound deficiency of alpha-acetylglucosaminidase activity in organs and skin fibroblasts from type-B patients. Proc Natl Acad Sci USA 69:1720–1722
Raimondi AJ, Bailey OT, McClone DG, Lawson RF, Echeverry A (1973) The pathophysiology and morphology of murine hydrocephalus in Hy-3 and ch mutants. Surg Neurol 1:50–55
Risdon RA, Turner DR (1980) Atlas of renal pathology, vol 2: Congenital malformations of the kidney. Lippincott, Philadelphia, pp 11–15
Rosenberg L, Schubert M (1970) The protein-polysaccharides in cartilage. The immunochemistry and biochemistry of connective tissue and its diseased state. Karger, Basel, pp 1–60 (Rheumatology, vol 3)
Saunders AM (1964) Histochemical identification of acid mucopolysaccharides with acridine orange. J Histochem Cytochem 12:164–170
Scott JE, Dorling J (1965) Differential staining of acid glycosaminoglycans (mucopolysaccharides) by alcian blue in salt solutions. Histochemistry 5:221–233
Seegmiller R, Fraser FC, Sheldon H (1971) A new chondrodystrophic mutant in mice. J Cell Biol 48:580–593
Seegmiller R, Ferguson CC, Sheldon H (1972) Studies on cartilage. VI. A genetically determined defect in tracheal cartilage. J Ultrastruct Res 38:288–301
Silberberg R, Rimoin DC, Rosenthal RE, Hasler MB (1972) Ultrastructure of cartilage in the Hurler and Sanfilippo syndromes. Arch Pathol 94:500–510
Serafini-Fracassina A, Smith JW (1974) The structure and biochemistry of cartilage. Churchill Livingstone, London, pp 126–176
Sobel H (1971) Metabolism of hyaluronic acid in the skin of aging mice. J Gerontol 26:555–557
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Richardson, R.R. Congenital genetic murine (ch) hydrocephalus. Child's Nerv Syst 1, 87–99 (1985). https://doi.org/10.1007/BF00706688
Issue Date:
DOI: https://doi.org/10.1007/BF00706688