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. 1971 Aug 1;134(2):313–334. doi: 10.1084/jem.134.2.313

DEFECTS IN HEMATOPOIETIC DIFFERENTIATION IN NZB AND NZC MICE

Noel L Warner 1, Malcolm A S Moore 1
PMCID: PMC2139053  PMID: 4934499

Abstract

Hematopoietic stem cell activity in inbred NZB and NZC mice has been determined by transplantation and endogenous spleen colony assays. Whereas NZB mice show normal colony-forming unit (CFU) activity in the transplantation assay, they show markedly elevated endogenous CFU. NZC mice also show this markedly elevated endogenous CFU activity, but in the transplantation assay show only about 5–10% of normal CFU counts. When NZC stem cells are tested for CFU activity in irradiated recipients of the H-2d type, almost normal colony numbers occur. NZB stem cells however also cannot form colonies in NZC mice. These results suggest that NZC mice have a defect in the micro-environment of the spleen which renders them incapable of allowing transplanted CFU to form colonies. Genetic analysis of both the NZC defect as a CFU recipient, and the elevated endogenous count in NZB and NZC, shows that both are controlled by single recessive genes which are not linked to either coat color, agouti, H-2 or Ig loci. Of even more relevance is the finding that these hematopoietic abnormalities are not linked to the genes involved in controlling autoantibody formation to red cells in the NZB mice. These mice therefore appear to show two distinct hematopoietic abnormalities, the analysis of which may be of considerable value in understanding the detailed events of hematopoietic stem cell differentiation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BIELSCHOWSKY M., BIELSCHOWSKY F. OBSERVATIONS ON NZB/B1 MICE; DIFFERENTIAL FERTILITY IN RECIPROCAL CROSSES AND THE TRANSMISSION OF THE AUTO-IMMUNE HAEMOLYTIC ANAEMIA TO NZB/B1 X NZC/B1 HYBRIDS. Aust J Exp Biol Med Sci. 1964 Aug;42:561–568. [PubMed] [Google Scholar]
  2. Bielschowsky M., Goodall C. M. Origin of inbred NZ mouse strains. Cancer Res. 1970 Mar;30(3):834–836. [PubMed] [Google Scholar]
  3. Boggs D. R., Marsh J. C., Chervenick P. A., Bishop C. R., Cartwright G. E., Wintrobe M. M. Factors influencing hematopoietic spleen colony formation in irradiated mice. II. The effect of foreign materials. J Exp Med. 1967 Nov 1;126(5):851–870. doi: 10.1084/jem.126.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Curry J. L., Trentin J. J. Hemopoietic spleen colony studies. IV. Phytohemagglutinin and hemopoietic regeneration. J Exp Med. 1967 Nov 1;126(5):819–832. doi: 10.1084/jem.126.5.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. HOLMES M. C., BURNET F. M. THE NATURAL HISTORY OF AUTOIMMUNE DISEASE IN NZB MICE. A COMPARISON WITH THE PATTERN OF HUMAN AUTOIMMUNE MANIFESTATIONS. Ann Intern Med. 1963 Sep;59:265–276. doi: 10.7326/0003-4819-59-3-265. [DOI] [PubMed] [Google Scholar]
  6. Hanna M. G., Jr, Nettesheim P., Fisher W. D., Peters L. C., Francis M. W. Serum alpha globulin fraction: survival-and-recovery effect in irradiated mice. Science. 1967 Sep 22;157(3795):1458–1461. doi: 10.1126/science.157.3795.1458. [DOI] [PubMed] [Google Scholar]
  7. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  8. Marsh J. C., Boggs D. R., Bishop C. R., Chervenick P. A., Cartwright G. E., Wintrobe M. M. Factors influencing hematopoietic spleen colony formation in irradiated mice. I. The normal pattern of endogenous colony formation. J Exp Med. 1967 Nov 1;126(5):833–849. doi: 10.1084/jem.126.5.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McCulloch E. A., Siminovitch L., Till J. E., Russell E. S., Bernstein S. E. The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sld. Blood. 1965 Oct;26(4):399–410. [PubMed] [Google Scholar]
  10. Morton J. I., Siegel B. V. Radiation sensitivity of New Zealand black mice and the development of autoimmune disease and neoplasia. Proc Natl Acad Sci U S A. 1971 Jan;68(1):124–126. doi: 10.1073/pnas.68.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sutherland D. J., Till J. E., McCulloch E. A. A kinetic study of the genetic control of hemopoietic progenitor cells assayed in culture and in vivo. J Cell Physiol. 1970 Jun;75(3):267–274. doi: 10.1002/jcp.1040750302. [DOI] [PubMed] [Google Scholar]
  12. TILL J. E., MCCULLOCH E. A. REPAIR PROCESSES IN IRRADIATED MOUSE HEMATOPOIETIC TISSUE. Ann N Y Acad Sci. 1964 Mar 31;114:115–125. doi: 10.1111/j.1749-6632.1964.tb53566.x. [DOI] [PubMed] [Google Scholar]
  13. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  14. Vacek A., Davidová E. On the question of differences in the number of endogenous haemopoietic tissue colonies in the spleens of irradiated hairless and haired mice. Folia Biol (Krakow) 1969;17(3):197–204. [PubMed] [Google Scholar]
  15. Warner N. L., Wistar R., Jr Immunoglobulins in NZB-BL mice. I. Serum immunoglobulin levels and immunoglobulin class of erythrocyte autoantibody. J Exp Med. 1968 Jan 1;127(1):169–183. doi: 10.1084/jem.127.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]

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