Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

Miller, Robert D.; Hogg, J C; Ozaki, Jennifer H.; Gell, David A.; Jackson, Stephen; Riblet, Roy

doi:10.1073/pnas.92.23.10792

Cited by 53 publications

(20 citation statements)

References 45 publications

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“…Increased sensitivity to ␥-irradiation is also characteristic of scid mice. The wild-type allele at the Prkdc scid locus has been shown to function as a DNA repair gene, and the scid mutation confers a marked defect in ability to repair dsDNA damage (24,25,(41)(42)(43). Our studies demonstrate that irradiated NOD/LtSz-Rag1 null mice provide an excellent environment for human stem cell engraftment and permit longerterm studies compared with NOD/LtSz-scid mice.…”

Section: Discussionmentioning

confidence: 73%

NOD/LtSz-Rag1nullMice: An Immunodeficient and Radioresistant Model for Engraftment of Human Hematolymphoid Cells, HIV Infection, and Adoptive Transfer of NOD Mouse Diabetogenic T Cells

Shultz

Lang

Christianson

et al. 2000

The Journal of Immunology

147

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Development of a small animal model for the in vivo study of human immunity and infectious disease remains an important goal, particularly for investigations of HIV vaccine development. NOD/Lt mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation readily support engraftment with high levels of human hematolymphoid cells. However, NOD/LtSz-scid mice are highly radiosensitive, have short life spans, and a small number develop functional lymphocytes with age. To overcome these limitations, we have backcrossed the null allele of the recombination-activating gene (Rag1) for 10 generations onto the NOD/LtSz strain background. Mice deficient in RAG1 activity are unable to initiate V(D)J recombination in Ig and TCR genes and lack functional T and B lymphocytes. NOD/LtSz-Rag1null mice have an increased mean life span compared with NOD/LtSz-scid mice due to a later onset of lymphoma development, are radioresistant, and lack serum Ig throughout life. NOD/LtSz-Rag1null mice were devoid of mature T or B cells. Cytotoxic assays demonstrated low NK cell activity. NOD/LtSz-Rag1null mice supported high levels of engraftment with human lymphoid cells and human hemopoietic stem cells. The engrafted human T cells were readily infected with HIV. Finally, NOD/LtSz-Rag1null recipients of adoptively transferred spleen cells from diabetic NOD/Lt+/+ mice rapidly developed diabetes. These data demonstrate the advantages of NOD/LtSz-Rag1null mice as a radiation and lymphoma-resistant model for long-term analyses of engrafted human hematolymphoid cells or diabetogenic NOD lymphoid cells.

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Section: Discussionmentioning

confidence: 73%

NOD/LtSz-Rag1nullMice: An Immunodeficient and Radioresistant Model for Engraftment of Human Hematolymphoid Cells, HIV Infection, and Adoptive Transfer of NOD Mouse Diabetogenic T Cells

Shultz

Lang

Christianson

et al. 2000

The Journal of Immunology

147

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“…Interestingly, the Scid gene functioning in DNA repair has been mapped in the vicinity of TLSR16a (Miller et al, 1995;Hamatani et al, 1996). Mice lacking this gene show enhanced susceptibility to the induction of thymic lymphomas by x-irradiation (Lieberman et al, 1992).…”

Section: Two Loci Showing Frequent Allelic Lossmentioning

confidence: 99%

Allelic loss analysis of γ-ray-induced mouse thymic lymphomas: two candidate tumor suppressor gene loci on chromosomes 12 and 16

et al. 1998

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A total of 429 g-ray-induced thymic lymphomas were obtained from F 1 and backcross mice between BALB/c and MSM strains, about a half of which carried a p53-de®cient allele. A genome-wide allelic loss analysis has revealed two loci exhibiting frequent allelic losses but no allelic preference, one is localized within a 2.9 cM region between D12Mit53 and D12Mit279 loci on chromosome 12, and the other is near the D16Mit122/D16Mit162 loci on chromosome 16. The frequency of allelic loss in the D12Mit279 region is 62% and does not dier in tumors between the presence and absence of the p53-de®cient allele. In contrast, the loss frequency of D16Mit122 is raised by the existence of p53-de®cient allele: 62% for p63(7/+) and 13% for p53(+/+), suggesting cooperative function of the two losses. The D12Mit279 and D16Mit122 regions probably harbor dierent types of tumor suppressor gene that play key roles in lymphoma development.

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“…[319][320][321][322][323] Dysfunctional Prkdc genes effect deactivation of a DNA recombinase enzyme, resulting in inability to express rearranged antigen receptors 324,325 and thus innate deficiency in humoral and cellular immunity, with scid mice lacking functional T and B lymphocytes. 326 This model and those following in the remainder of this section have been used extensively to study normal human haematopoiesis, but for the purposes of this review the authors will focus only on human AML xenografts and refer the reader to some excellent reviews for the latter.…”

Section: Nude Modelsmentioning

confidence: 99%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

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From the early inception of the transplant models through to contemporary genetic and xenograft models, evolution of murine leukaemic model systems have been critical to our general comprehension and treatment of cancer, and, more specifically, disease states such as acute myelogenous leukaemia (AML). However, even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Thus, in the absence of definitive in vitro models which precisely recapitulate the in vivo setting of human AMLs and failure of significant numbers of new drugs late in clinical trials, it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. While various model systems are described and discussed in the literature from initial transplant models such as BNML and spontaneous murine leukaemia virus models, to the more definitive genetic and clinically significant NOD/SCID xenograft models, there exists no single compendium which directly assesses, reviews or compares the relevance of these models. Thus, the function of this article is to provide clinicians and experimentalists a chronological, comprehensive appraisal of all AML model systems, critical discussion on the elucidation of their roles in our understanding of AML and consideration to their efficacy in the development of AML chemotherapeutics.

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Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

Abstract: The (27)(28)(29)(30). Furthermore, the scid-related defects in DNA repair and V(D)J recombination were also complemented by transfecting V3 cells with yeast artificial chromosomes (YACs) containing the

Cited by 53 publications

References 45 publications

NOD/LtSz-Rag1nullMice: An Immunodeficient and Radioresistant Model for Engraftment of Human Hematolymphoid Cells, HIV Infection, and Adoptive Transfer of NOD Mouse Diabetogenic T Cells

NOD/LtSz-Rag1nullMice: An Immunodeficient and Radioresistant Model for Engraftment of Human Hematolymphoid Cells, HIV Infection, and Adoptive Transfer of NOD Mouse Diabetogenic T Cells

Allelic loss analysis of γ-ray-induced mouse thymic lymphomas: two candidate tumor suppressor gene loci on chromosomes 12 and 16

Animal models of acute myelogenous leukaemia – development, application and future perspectives

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