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Mouse models with human immunity and their application in biomedical research.

Zhang B, Duan Z, Zhao Y - J. Cell. Mol. Med. (2008)

Bottom Line: Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism.Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved.The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)() mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

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The frequencies of cell leakiness in various immunodeficient mouse strains with aging.
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fig01: The frequencies of cell leakiness in various immunodeficient mouse strains with aging.

Mentions: SCID mice are defective in DNA repair because of a mutation in DNA-dependent protein kinase (DNA-PK) in the CB-17 inbred mouse strain [25, 26], therefore they lack productive rearrangement of T cell receptor and immunoglobulin genes, which subsequently results in the deficiency of T and B cells [27]. The lack of functional T and B cells in SCID mice contributes to the acceptance of allogeneic or xenogeneic grafts without severe rejection [1, 28, 29]. However, SCID mice have a radiation repair deficiency and an uncomplete block of VDJ recombination, so some old SCID mice may become ‘leaky’ mice depending on antigen stimulation (Fig. 1). In addition, residual innate immunity including complement, natural killer (NK) cells, macrophages and granulocytes remains somewhat intact in SCID mice, which may limit the grafting efficiency of xenogeneic cells and tissues (Table 1) [30, 31]. Many efforts have been made to develop modified SCID mice with more deficient innate immunity such as severely reduced NK cell function and phagocytosis by genetic crossings with inbred or other mutant strains of mice [32, 33].


Mouse models with human immunity and their application in biomedical research.

Zhang B, Duan Z, Zhao Y - J. Cell. Mol. Med. (2008)

The frequencies of cell leakiness in various immunodeficient mouse strains with aging.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496103&req=5

fig01: The frequencies of cell leakiness in various immunodeficient mouse strains with aging.
Mentions: SCID mice are defective in DNA repair because of a mutation in DNA-dependent protein kinase (DNA-PK) in the CB-17 inbred mouse strain [25, 26], therefore they lack productive rearrangement of T cell receptor and immunoglobulin genes, which subsequently results in the deficiency of T and B cells [27]. The lack of functional T and B cells in SCID mice contributes to the acceptance of allogeneic or xenogeneic grafts without severe rejection [1, 28, 29]. However, SCID mice have a radiation repair deficiency and an uncomplete block of VDJ recombination, so some old SCID mice may become ‘leaky’ mice depending on antigen stimulation (Fig. 1). In addition, residual innate immunity including complement, natural killer (NK) cells, macrophages and granulocytes remains somewhat intact in SCID mice, which may limit the grafting efficiency of xenogeneic cells and tissues (Table 1) [30, 31]. Many efforts have been made to develop modified SCID mice with more deficient innate immunity such as severely reduced NK cell function and phagocytosis by genetic crossings with inbred or other mutant strains of mice [32, 33].

Bottom Line: Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism.Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved.The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)() mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

Show MeSH
Related in: MedlinePlus