Naked mouse

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A naked mouse
Naked mouse from above
Naked mouse from the front
Athymic mouse with implanted human prostate carcinoma (LNCaP cell line).

The nude mouse , also known as the thymus aplastic mouse or athymic mouse , is a genetic mutant of the house mouse with a missing thymus . The phenotype (appearance) of the mouse is expressed by a lack of body hair , from which its name is derived. The nude mouse is an extremely important model organism for research .

Properties and use

The underlying genetic defect not only causes the absence of body hair, but also a lack of development of the thymus combined with a strong reduction in the number of T lymphocytes . In the thymus, the conversion of thymocytes (pre-T lymphocytes) into T lymphocytes (T cells) takes place. The number of B cells in the lymphocytes is normal in the nude mouse, while mature T lymphocytes are absent. Due to the considerable lack of T-lymphocytes, the nude mouse has a severely restricted immune system, which makes it an ideal host for homologous and xenogeneic (so-called xenografts ) transplants . There is no immune system-induced rejection reaction in the nude mouse against xenografts, for example tissue parts of malignant tumors from other living beings (mostly of human origin) .

Xenotransplants in the nude mouse are generally used in research, for example to develop new methods in the diagnosis and treatment of cancer .

The absence of the thymus causes a failure in the nude mouse:

  1. the production of antibodies (CD4 + T helper cells are required for this)
  2. the cell-mediated immune response (requires CD4 + T helper cells and / or cytotoxic T cells )
  3. delayed hypersensitivity (requires CD4 + T white blood cells)
  4. the elimination of virulent or malignant cells (requires cytotoxic T cells)
  5. the rejection of foreign tissue (requires CD4 + T helper cells and cytotoxic T cells)

The weak immune system of nude mice requires special conditions when keeping the animals. In addition to a special food, dust-free bedding in an environment that is as germ-free as possible ( laminar flow cages ), temperatures around 25 ° C and a humidity of 65% are necessary for keeping the animals.

genetics

Nude mice have a spontaneous deletion in the FOXN1 gene. People with mutations in FOXN1 are also athymic and have an immunodeficiency. Knockout mice with a deletion in FOXN1 show the same phenotype. Female nude mice have underdeveloped mammary glands and are therefore unable to adequately breastfeed their young. Male nude mice are therefore mated with heterozygous females.

history

In 1961, athymic mice arose in Glasgow as a result of a spontaneous mutation in albino mice. The mutation is inherited in an autosomal recessive manner . Hairlessness and thymic aplasia (the absence of the thymus) are inseparable characteristics. In 1971 Rygaard and Povlsen carried out the first successful transplantation of a human colon carcinoma into the nude mouse. In 1972, tumor cell lines that had grown in a cell culture could be transplanted into the nude mouse. With the treatment of Burkitt's lymphoma transplanted in nude mice , a new path in the preclinical development of cytostatic drugs was broken for the first time in 1974 .

Individual evidence

  1. ^ J. Sprent: Migration and Lifespan of Circulating B-Lymphocytes of Nude (nu / nu) Mice. In: Proc. First intern. Workshop Nude Mice G. Fischer Verlag, New York, Stuttgart, 1974, pp. 11-12.
  2. ↑ a b J. Schueler: Development and characterization of human tumor models by orthotopic implantation. Dissertation, FU Berlin, 1999.
  3. ↑ HP Fortmeyer: Thymusaplastic mouse (nu / nu) Thymusaplastic rat (rnu / rnu) - keeping, breeding, experimental models. In: Series of experimental animal studies 8 , P. Parey publishing house, Berlin, Hamburg, 1981.
  4. ↑ HP Fort Meyer, G. Bastert : Breeding and Keeping of nu / nu mice. In: Z. experimental animal. 19/1977, p. 339.
  5. ↑ EM Panterlouris: Absence of the thymus in a mouse mutant. In: Nature 217/1968, p. 370.
  6. ^ SP Flanagan: "Nude", a new hairless gene with pleiotropic effects in the mouse. In: Genet Res 8/1966, pp. 295-309. PMID 5980117
  7. ↑ CO Povlsen, J. Rygaard: Heterotransplantation of human adenocarcinoma of the colon and rectum to the mouse of the mutant nude. A study of nine consecutive transplantations. In: Acta Pathol Microbiol Scand 79/1971, pp. 159-69.
  8. ↑ J. Rygaard: Immunobiology of the mouse mutant "Nude". Preliminary investigations. In: Acta Pathol Microbiol Scand 77/1969, pp. 761-2. PMID 4911130
  9. ^ BC Giovanella et al .: Development of invasive tumors in the nude mouse after injection of cultured human melanoma cells. In: J Natl Cancer Inst . 48/1972, pp. 1531-33.
  10. ↑ CO Povlsen, J. Rygaard: Effects of Cyclophosphamide (Endoxan R) on a Burkitt's Lymphoma serially grown in nude mice. In: Proceedings of the first international workshop on nude mice. Verlag Gustav Fischer, Stuttgart, New York, 1974, pp. 285-92.

literature

  • J. Fogh, BC Giovanella (Editors): The Nude Mouse in Experimental and Clinical Research (Vol.1). Academic Press, 1978, ISBN 0-12-261860-2
  • J. Fogh, BC Giovanella (Editors): The Nude Mouse in Experimental and Clinical Research (Vol.2). Academic Press, 1982, ISBN 0-12-261862-9
  • Laboratory Animals: Origin of Nude Mouse. In: Nature 224/1969, pp. 114-5.
  • BJ Braakhuis et al .: The potential of the nude mouse xenograft model for the study of head and neck cancer. In: Archives of oto-rhino-laryngology 239/1984, pp. 69-79. PMID 6691837
  • T. Devos et al .: Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique. In: Transplantation , 85/2008, pp. 640-4. PMID 18347545
  • D. Kong et al .: Establishment and characterization of human pancreatic adenocarcinoma cell line in tissue culture and the nude mouse. In: Tissue & Cell 39/2007, pp. 217-223. PMID 17560620
  • S. Loisel et al .: Establishment of a novel human B-CLL-like xenograft model in nude mouse. In: Leukemia Research 29/2005, pp. 1347-52.
  • L. Miers et al .: Implantation of different malignant human cell lines in an athymic mouse does not alter success and growth rates of either xenograft. In: Cancer Biotherapy and Radiopharmaceuticals 20/2005, pp. 614-619. PMID 16398613
  • SC Yeung et al .: Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. In: J Clin Endocrinol Metab 92/2007, pp. 2902-9. PMID 17550961

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