Advertisement

Virchows Archiv A

, Volume 395, Issue 2, pp 117–131 | Cite as

Value of an animal model for trisomy

  • Alfred Gropp
Review

Summary

Problems related to the developmental pathology of fetal aneuploidy are amenable to systematic investigation in a mouse model of autosomal trisomy. With a breeding design of one parent doubly heterozygous for two partially homologous Robertsonian metacentrics, some of the monosomies and all nineteen trisomies of the mouse can be studied. Monosomies are eliminated either before or shortly after implantation. Some trisomies do not survive a first critical phase of organogenesis on days 11 to 12 of fetal development, others such as Ts 12 to 14, 16, 18, and 19 have a lifespan until or beyond birth. A critical situation of long duration is caused in late development by hypoplasia of the placental labyrinth and ensuing impairment of metabolic exchange and of oxygen supply to the fetus. Model type morphogenetic analyses of anomalies (e.g. cranio-cerebral, cardio-vascular), are possible in Ts 1, 12, 14, 19, and others, and Ts 16 of the mouse is considered to be a close and natural model of human trisomy 21. The eventual breakdown and death of the aneuploid organism is inevitable. However, the introduction of monosomic or the transfer of trisomic haemopoietic stem cells to irradiated recipients is a means of rescuing the aneuploid cells and tissues with longer survival. Under these conditions isolated trisomic haemapoiesis can show almost complete and near-normal maturation, at least in trisomies 12 and 19. In other trisomies (e.g., 13 and 16) stem cell defects impair such reconstitution.

The experimental induction of mouse aneuploidy is a powerful technique which allows us to fill gaps in our existing knowledge of human trisomy, and suggests new lines of research. These are the major benefits of an experimental model.

Key words

Man Mouse Developmental genetics Monosomy Trisomy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boué JG, Boué A (1976) Chromosomal anomalies in early spontaneous abortion. In: A. Gropp, K. Benirschke (eds) Curr Top Pathol 62: Developmental Biology and Pathology. Springer, Berlin Heidelberg New York, pp 193–208Google Scholar
  2. Boué JG, Boué A, Lazar P (1975) Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. Teratology 12:11–16Google Scholar
  3. Cox DR, Epstein LB, Epstein CJ (1980) Genes coding for sensitivity to interferon (IfRec) and soluble superoxide dismutase (SOD-1) are linked in mouse and man and map to mouse chromosome 16. Proc Natl Acad Sci USA 77:2168–2172Google Scholar
  4. Cox DR, Goldblatt D, Epstein CJ (1981) Chromosomal assignment of mouse PRGS: Further evidence for homology between mouse chromosome 16 and human chromosome 21. Am J Num Genet 33:145AGoogle Scholar
  5. Cox DR, Smith SA, Zamora T, Epstein LB, Epstein CJ (1982) Mouse trisomy 16 as an animal model of Down syndrome: formation of viable adult trisomy 16↔diploid chimeras. Clin. Res. 30 (In press)Google Scholar
  6. Dyban AP, Baranov VS (1978) Cytogenetics of mammalian development (in Russian). Problemi Biologii Razvitija. Moskwa: Izdatelstwo “Nauka”, p 216Google Scholar
  7. Eicher EM, Coleman LC (1977) Influence of gene duplication and X-inactivation on mouse mitochondrial malic enzyme activity and electrophoretic patterns. Genetics 85:647–658Google Scholar
  8. Epstein CJ, Travis B (1979) Preimplantation lethality of monosomy for mouse chromosome 19. Nature (Lond) 280:144–145Google Scholar
  9. Epstein CJ, Tucker G, Travis B, Gropp A (1977) Gene dosage for isocitrate dehydrogenase in mouse embryos trisomic for chromosome 1. Nature (Lond) 267:615–616Google Scholar
  10. Epstein CJ, Cox DR, Epstein LB (1979) Synteny of the mouse genes for soluble superoxide dismutase (SOD-1) and the species-specific sensitivity to interferon (Avg). Am J Hum Genet 31:46AGoogle Scholar
  11. Epstein CJ, Epstein LB, Cox D, Weil J (1981) Functional implications of gene dosage effects in trisomy 21. In: GR Burgio, M Fraccaro, L Tiepolo, U Wolf (eds) Trisomy 21 Hum Genet Suppl 2. Springer, Berlin Heidelberg New York, pp 155–171Google Scholar
  12. Ford CE (1972) Gross genome unbalance in mouse spermatozoa: does it influence the capacity to fertilize? In: RA Beatty, S Gluecksohn-Waelsch (eds) The genetics of the spermatozoon. Edinburgh and New York:University of Edinburgh, pp 359–369Google Scholar
  13. Francke U, Taggart RT (1979) Assignment of the gene for cytoplasmic superoxide dismutase (Sod-1) to a region of chromosome 16 and of Hprt to a region of the X chromosome in the mouse. Proc Natl Acad Sci USA 76:5230–5233Google Scholar
  14. Francke U, Lalley PA, Moss W, Ivy J, Minna JD (1977) Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2. Cytogenet Cell Genet 19:57–84Google Scholar
  15. Fundele R, Bücher Th, Gropp A, Winking H (1981) Enzyme patterns in trisomy 19 of the mouse. Dev Gen 2:291–303Google Scholar
  16. Grabowski CT (1977) Altered electrolyte and fluid balance. In: JG Wilson, FC Fraser (eds), vol. II, Handbook of teratology. Plenum Press, New York, pp 153–170Google Scholar
  17. Green MC (1981) Genetic variants and strains of the laboratory mouse. G. Fischer, Stuttgart, pp 8–282Google Scholar
  18. Grohé G, Gropp A (1980) Research note (on Ts 19). Mouse News Letter 63:23Google Scholar
  19. Gropp A (1974) Animal model: Autosomal trisomies in fetal mice. Exencephaly in mice with trisomy 12. Am J Pathol 77:539–542Google Scholar
  20. Gropp A (1981) Clinical and experimental pathology of fetal wastage. In: K Semm, L Mettler (eds) Human reproduction. Excerpta Medica, Amsterdam. ICS No 551, pp 208–216Google Scholar
  21. Gropp A (1978) Relevance of phases of development for expression of abnormality. Perspectives drawn from experimentally induced chromosome aberrations. (Life Sciences Report 10) Dahlem Konferenzen, Berlin, pp 85–110Google Scholar
  22. Gropp A (1971) Reproductive failure due to fetal aneuploidy in mice. VII World Congr. on Fertility and sterility, Tokyo/Kyoto. Excerpta Medica, Amsterdam. ICS No 234, pp 326–330Google Scholar
  23. Gropp A, Grohé G (1981) Strain background dependence of expression of chromosome triplication in the mouse embryo. Abstract. Hereditas 94:7–8Google Scholar
  24. Gropp A, Herbst EW, Nielsén K (1982) In vivo and in vitro assays of trisomic cells isolated from the fetal organism or rescued by transfer to non-trisomic hosts. In: D Neubert HJ Merker (eds), Culture techniques in prenatal toxicology. De Gruyter Berlin (In press)Google Scholar
  25. Gropp A, Winking H (1981) Robertsonian translocations: Cytology, meiosis, segregation patterns and biological consequences of heterozygosity. Symp Zool Soc Lond 47:141–181Google Scholar
  26. Gropp A, Winking H, Zech L, Müller HJ (1972) Robertsonian chromosomal variation and identification of metacentric chromosomes in feral mice. Chromosoma (Berlin) 39:265–288Google Scholar
  27. Gropp A, Kolbus U, Giers D (1975) Systematic approach to the study of trisomy in the mouse. II. Cytogenet Cell Genet 14:42–62Google Scholar
  28. Gropp D, Winking H, Gropp A (1981) Research note (on Ts 18). Mouse News Letter No 65:32Google Scholar
  29. Hamerton JL, Canning N, Ray M, Smith S (1975) A cytogenetic survey of 14,069 newborn infants. Clin Genet 8:223–243Google Scholar
  30. Herbst EW, Pluznik DH, Gropp A, Uthgenannt H (1981) Trisomie hemopoietic stem cells of fetal origin restore hemopoiesis in lethally irradiated mice. Science 211:1175–1177Google Scholar
  31. Herbst EW, Gropp A, Nielsén K, Hoppe H, Freymann M, Pluznik DH (1982) Reduced ability of mouse trisomy 16 stem cells to restore hemopoiesis in lethally irradiated animals. In: S Baum, GD Ledney, A Khan (eds), Experimental hematology today. Karger, Basel (In press)Google Scholar
  32. Hoehn H, Simpson M, Bryant EM, Rabinovitch PS, Salk D, Martin GM (1980) Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures. Am J Med Genet 7:141–154Google Scholar
  33. Hongell K, Gropp A (1982) Trisomy 13 in the mouse. Teratology (In press)Google Scholar
  34. Hongell K, Herbst EW, Gropp A (1982) Transplantation of mixed trisomie and normal fetal hemopoietic stem cells of the mouse to irradiated hosts. Dev Genet (In press)Google Scholar
  35. Klose J, Putz B (1982) Analysis of two-dimensional protein patterns from mouse embryos with different trisomies (developmental stages/developmental impairment). Proc Natl Acad Sci (USA) (In press)Google Scholar
  36. Krone W, Wolf U (1977) Chromosome variation and gene action. Hereditas 86:31–36Google Scholar
  37. Magnuson T, Smith SA Epstein CJ (1982) The development of monosomy 19 mouse embryos. J Embryol Exp Morphol (In press)Google Scholar
  38. Miller DA, Miller OJ (1981) Cytogenetics. In: The mouse in biomedical research, vol I. Academic Press, New York London Toronto San Francisco, pp 241–261Google Scholar
  39. Milunski A, Atkins L (1977) The frequency of chromosomal abnormalities diagnosed prenatally. In: E Hootz, IH Porter (eds) Population cytogenetics. Academic Press, New York-San Francisco-London, pp 11–25Google Scholar
  40. Miyabara Sh, Gropp A, Winking H (1982) Trisomy 16 in the mouse fetus associated with generalized edema, cardiovascular and urinary tract anomalies. Teratology 25 (In press)Google Scholar
  41. Nielsén K, Marcus M, Gropp A (1982) In vitro growth kinetics of mouse trisomies 12 and 19. J Cell Biol (subm)Google Scholar
  42. Paton GR, Silver MF, Allison AC (1974) Comparison of cell cycle time in normal and trisomic cells. Humangenetic 23:173–182Google Scholar
  43. Pearson PL, Roderick TH (1978) Report of the committee on comparative mapping. Human Gene Mapping 5. Cytogenet Cell Genet 22:150–162Google Scholar
  44. Pexieder T, Miyabara Sh, Gropp A (1981) Congenital heart disease in experimental (fetal) mouse trisomies: Incidence. In: Mechanisms of cardiac morphogenesis and teratogenesis. Perspec Cardiovasc Res 5: (T Pexieder, ed), Raven Press, New York, pp 389–399Google Scholar
  45. Pluznik DH, Herbst EW, Lenz R, Seilin D, Hertogs CF, Gropp A (1981) Controlled production of trisomic hematopoietic stem cells: An experimental tool in hematology and immunology. In:SJ Baum, GD Ledney, A Khan (eds), Experimental hematology today. Karger, Basel, pp 3–11Google Scholar
  46. Polani PE, Adinolfi, M (1980) Annotations: Chromosome 21 of man, 22 of the great apes and 16 of the mouse. Dev Med Child Neurol 22:223–225Google Scholar
  47. Putz B, Morriss-Kay G (1981) Abnormal neuralfold development in trisomy 12 and trisomy 14 mouse embryos. I. Scanning electron microscopy. J Embryol exp Morphol 66:141–158 1981Google Scholar
  48. Putz B, Krause G, Garde T, Gropp A (1980) A comparison between trisomy 12 and vitamin A induced exencephaly and associated malformations in the mouse embryo. Virchows Arch (Path Anat) 368:65–80Google Scholar
  49. Render H (1981) Pathology of trisomy 21- with particular reference to persistent common atrioventricular canal of the heart. In: GR Burgio, M Fraccaro, L Tiepolo, U Wolf (eds) Trisomy 21. Hum Genet, Suppl 2. Springer, Berlin-Heidelberg-New York, pp 57–73Google Scholar
  50. Schneider EL, Epstein CJ (1972) Replication rate and lifespan of cultured fibroblasts in Down's syndrome. Proc Soc Exp Biol Med 141:1092–1094Google Scholar
  51. Stolla R, Gropp A (1974) Variation of the DNA content of morphologically normal and abnormal spermatozoa in mice susceptible to irregular meiotic segregation. J Reprod Fert 38:335–346Google Scholar
  52. Tettenborn U, Gropp A (1970) Meiotic non-disjunction in mice and mouse hybrids. Cytogenetics 9:272–283Google Scholar
  53. White BJ, Tjio J-H, Water LC van de, Crandall C (1974a) Trisomy 19 in the laboratory mouse. I. Frequency in different crosses at specific developmental stages and relationship of trisomy to cleft palate. Cytogenet Cell Genet 13:217–231Google Scholar
  54. Trisomy 19 in the laboratory mouse. II. Intra-uterine growth and histological studies of trisomies and their normal littermates. Cytogenet Cell Genet 13:232–245 (1974b)Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Alfred Gropp
    • 1
  1. 1.Institut für Pathologie der Medizinischen Hochschule LübeckLübeckFederal Republic of Germany

Personalised recommendations