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. 1971 Mar 1;48(3):580–593. doi: 10.1083/jcb.48.3.580

A NEW CHONDRODYSTROPHIC MUTANT IN MICE

Electron Microscopy of Normal and Abnormal Chondrogenesis

R Seegmiller 1, F C Fraser 1, H Sheldon 1
PMCID: PMC2108112  PMID: 4100752

Abstract

The occurrence of a new mutation affecting cartilage and bone in mice is reported. The gene is lethal, shows autosomal recessive inheritance, and has high penetrance. It is not allelic to shorthead and probably not to phocomelia or achondroplasia. It results in a foreshortened face, cleft palate, defective trachea, and shortened long bones with flared metaphyses. Chondrocytes of epiphyseal cartilage from the mutant are not aligned in columns, and there is a decrease in the usual staining of the cartilage matrix. Electron microscope observations show large, wide collagen fibrils with "native" banding in the matrix of mutant cartilage, which are not present in normal cartilage. Possible explanations for the expression of this genetic disorder of cartilage development are put forward.

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Selected References

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  1. Amuso S. J. Diastrophic dwarfism. J Bone Joint Surg Am. 1968 Jan;50(1):113–122. doi: 10.2106/00004623-196850010-00007. [DOI] [PubMed] [Google Scholar]
  2. Anderson H. C. Electron microscopic studies of induced cartilage development and calcification. J Cell Biol. 1967 Oct;35(1):81–101. doi: 10.1083/jcb.35.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bona C., Stănescu V., Streja D. Differential regional distribution of mucopolysaccharides in the human epiphyseal cartilage matrix in normal and pathologic conditions. Virchows Arch Pathol Anat Physiol Klin Med. 1967 Jun 12;342(3):274–281. doi: 10.1007/BF00960597. [DOI] [PubMed] [Google Scholar]
  4. Bonucci E. Fine structure of early cartilage calcification. J Ultrastruct Res. 1967 Sep;20(1):33–50. doi: 10.1016/s0022-5320(67)80034-0. [DOI] [PubMed] [Google Scholar]
  5. Bowness J. M. Present concepts of the role of ground substance in calcification. Clin Orthop Relat Res. 1968 Jul-Aug;59:233–247. [PubMed] [Google Scholar]
  6. CAMERON D. A., ROBINSON R. A. Electron microscopy of cartilage and bone matrix at the distal epiphyseal line of the femur in the newborn infant. J Biophys Biochem Cytol. 1956 Jul 25;2(4 Suppl):253–260. doi: 10.1083/jcb.2.4.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chacko S., Holtzer S., Holtzer H. Suppression of chondrogenic expression in mixtures of normal chondrocytes and BUDR-altered chondrocytes grown in vitro. Biochem Biophys Res Commun. 1969 Jan 27;34(2):183–189. doi: 10.1016/0006-291x(69)90629-9. [DOI] [PubMed] [Google Scholar]
  8. Cox R. W., Grant R. A. The structure of the collagen fibril. Clin Orthop Relat Res. 1969 Nov-Dec;67:172–187. [PubMed] [Google Scholar]
  9. Engfeldt B., Hjertquist S. O. The effect of various fixatives on the preservation of acid glycosaminoglycans in tissues. Acta Pathol Microbiol Scand. 1967;71(2):219–232. doi: 10.1111/j.1699-0463.1967.tb05160.x. [DOI] [PubMed] [Google Scholar]
  10. FEWER D., THREADGOLD J., ANDSHELDON H. STUDIES ON CARTILAGE. V. ELECTRON MICROSCOPIC OBSERVATIONS ON THE AUTORADIOGRAPHIC LOCALIZATION OF S35 IN CELLS AND MATRIX. J Ultrastruct Res. 1964 Aug;11:166–172. doi: 10.1016/s0022-5320(64)80100-3. [DOI] [PubMed] [Google Scholar]
  11. FITCH N. A mutation in mice producing dwarfism, brachycephaly, cleft palate and micromelia. J Morphol. 1961 Sep;109:141–149. doi: 10.1002/jmor.1051090203. [DOI] [PubMed] [Google Scholar]
  12. Ford J. K., Eyring E. J., Anderson C. E. Thallium chondrodystrophy in chick embryos. An histological and biochemical investigation. J Bone Joint Surg Am. 1968 Jun;50(4):687–700. doi: 10.2106/00004623-196850040-00004. [DOI] [PubMed] [Google Scholar]
  13. GODMAN G. C., PORTER K. R. Chondrogenesis, studied with the electron microscope. J Biophys Biochem Cytol. 1960 Dec;8:719–760. doi: 10.1083/jcb.8.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glauert A. M., Fell H. B., Dingle J. T. Endocytosis of sugars in embryonic skeletal tissues in organ culture. II. Effect of sucrose on cellular fine structure. J Cell Sci. 1969 Jan;4(1):105–131. doi: 10.1242/jcs.4.1.105. [DOI] [PubMed] [Google Scholar]
  15. Grant R. A., Cox R. W., Horne R. W. The structure and assembly of collagen fibrils. II. An electron-microscope study of cross-linked collagen. J R Microsc Soc. 1967;87(1):143–155. doi: 10.1111/j.1365-2818.1967.tb04499.x. [DOI] [PubMed] [Google Scholar]
  16. Hirschman A., Dziewiatkowski D. D. Protein-polysaccharide loss during endochondral ossification: immunochemical evidence. Science. 1966 Oct 21;154(3747):393–395. doi: 10.1126/science.154.3747.393. [DOI] [PubMed] [Google Scholar]
  17. Hirschman A., Silverstein D. The effect of proteolytic enzymes and hyaluronidase in vitro on the calcification mechanism of epiphyseal cartilage. Proc Soc Exp Biol Med. 1968 Dec;129(3):675–678. doi: 10.3181/00379727-129-33394. [DOI] [PubMed] [Google Scholar]
  18. Korhonen L. K., Lindholm K. Effect of histological fixation on carbohydrate-rich tissue compounds and their periodate consumption. Histochemie. 1969 Apr 17;18(1):87–96. doi: 10.1007/BF00309905. [DOI] [PubMed] [Google Scholar]
  19. LAMY M., MAROTEAUX P. [Diastrophic nanism]. Presse Med. 1960 Nov 23;68:1977–1980. [PubMed] [Google Scholar]
  20. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lane P. W., Dickie M. M. Three recessive mutations producing disproportionate dwarfing in mice: achondroplasia, brachymorphic, and stubby. J Hered. 1968 Sep-Oct;59(5):300–308. doi: 10.1093/oxfordjournals.jhered.a107725. [DOI] [PubMed] [Google Scholar]
  22. Levenson G. E. The effect of ascorbic acid on monolayer cultures of three types of chondrocytes. Exp Cell Res. 1969 May;55(2):225–228. doi: 10.1016/0014-4827(69)90484-4. [DOI] [PubMed] [Google Scholar]
  23. Luscombe M., Phelps C. F. Action of degradative enzymes on the light fraction of bovine septa protein polysaccharide. Biochem J. 1967 Apr;103(1):103–109. doi: 10.1042/bj1030103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MATHEWS M. B., LOZAITYTE I. Sodium chondroitin sulfate-protein complexes of cartilage. I. Molecular weight and shape. Arch Biochem Biophys. 1958 Mar;74(1):158–174. doi: 10.1016/0003-9861(58)90210-8. [DOI] [PubMed] [Google Scholar]
  25. Mathews M. B., Decker L. The effect of acid mucopolysaccharides and acid mucopolysaccharide-proteins on fibril formation from collagen solutions. Biochem J. 1968 Oct;109(4):517–526. doi: 10.1042/bj1090517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matukas V. J., Krikos G. A. Evidence for changes in protein polysaccharide associated with the onset of calcification in cartilage. J Cell Biol. 1968 Oct;39(1):43–48. doi: 10.1083/jcb.39.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McCallum H. M., Arbuthnott J. P. The inhibition of cartilage matrix production by glutamylaminoacetonitrile in vitro. Exp Mol Pathol. 1969 Oct;11(2):232–246. doi: 10.1016/0014-4800(69)90011-2. [DOI] [PubMed] [Google Scholar]
  28. Muir H. The structure and metabolism of mucopolysaccharides (glycosaminoglycans) and the problem of the mucopolysaccharidoses. Am J Med. 1969 Nov;47(5):673–690. doi: 10.1016/0002-9343(69)90163-6. [DOI] [PubMed] [Google Scholar]
  29. REVEL J. P., HAY E. D. AN AUTORADIOGRAPHIC AND ELECTRON MICROSCOPIC STUDY OF COLLAGEN SYNTHESIS IN DIFFERENTIATING CARTILAGE. Z Zellforsch Mikrosk Anat. 1963 Oct 8;61:110–144. doi: 10.1007/BF00341524. [DOI] [PubMed] [Google Scholar]
  30. SHELDON H., ROBINSON R. A. Studies on cartilage: electron microscope observations on normal rabbit ear cartilage. J Biophys Biochem Cytol. 1958 Jul 25;4(4):401–406. doi: 10.1083/jcb.4.4.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spicer S. S., Leppi T. J., Stoward P. J. Suggestions for a histochemical terminology of carbohydrate-rich tissue components. J Histochem Cytochem. 1965 Sep-Oct;13(7):599–603. doi: 10.1177/13.7.599. [DOI] [PubMed] [Google Scholar]
  32. THOMAS L. Reversible collapse of rabbit ears after intravenous papain, and prevention of recovery by cortisone. J Exp Med. 1956 Aug 1;104(2):245–252. doi: 10.1084/jem.104.2.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Toole B. P., Lowther D. A. The effect of chondroitin sulphate-protein on the formation of collagen fibrils in vitro. Biochem J. 1968 Oct;109(5):857–866. doi: 10.1042/bj1090857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wasteson A., Obrink B. Demonstration of an interaction between collagen and chondroitin sulphate. Biochim Biophys Acta. 1968 Nov 12;170(1):201–204. doi: 10.1016/0304-4165(68)90174-8. [DOI] [PubMed] [Google Scholar]
  35. Weston P. D., Barrett A. J., Dingle J. T. Specific inhibition of cartilage breakdown. Nature. 1969 Apr 19;222(5190):285–286. doi: 10.1038/222285b0. [DOI] [PubMed] [Google Scholar]
  36. Woodward C., Davidson E. A. Structure-function relationships of protein polysaccharide complexes: specific ion-binding properties. Proc Natl Acad Sci U S A. 1968 May;60(1):201–205. doi: 10.1073/pnas.60.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]

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