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Severe defect in thymic development in an insertional mutant mouse model

Assarsson, Erika; Chambers, Benedict J.; Hogstrand, Kari; Berntman, Emma LU ; Lundmark, Carin; Fedorova, Ludmila; Imreh, Stefan; Grandien, Alf; Cardell, Susanna and Rozell, Bjorn, et al. (2007) In Journal of Immunology 178(8). p.5018-5027
Abstract
Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature... (More)
Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature double-negative cells, indicating a block in thymic development at an early stage of differentiation. Consequently, Tg66 mice had reduced numbers of peripheral CD4(+) and CD8(+) T cells. Bone marrow from Tg66 mice readily reconstituted thyrni of irradiated wild-type as well as RAG-deficient mice. This indicates that the primary defect in Tg66 mice resided in nonhemopoietic stromal cells of the thymus. The phenotype is observed in mice heterozygous for the insertion and does not resemble any known mutations affecting thymic development. Preliminary studies in mice homozygous for transgene insertion reveal a more accelerated and pronounced phenotype suggesting a semidominant effect. The Tg66 mice may serve as a useful model to identify genes regulating thymic epithelial cell differentiation, thymic development, and function. (Less)
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Journal of Immunology
volume
178
issue
8
pages
5018 - 5027
publisher
American Association of Immunologists
external identifiers
  • wos:000245605300044
  • scopus:34247135522
ISSN
1550-6606
language
English
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yes
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08747b1a-0b53-4b65-a52b-714e61e0c6ff (old id 666424)
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http://www.jimmunol.org/cgi/reprint/178/8/5018
date added to LUP
2007-12-04 17:02:37
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2017-01-01 07:16:00
@article{08747b1a-0b53-4b65-a52b-714e61e0c6ff,
  abstract     = {Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature double-negative cells, indicating a block in thymic development at an early stage of differentiation. Consequently, Tg66 mice had reduced numbers of peripheral CD4(+) and CD8(+) T cells. Bone marrow from Tg66 mice readily reconstituted thyrni of irradiated wild-type as well as RAG-deficient mice. This indicates that the primary defect in Tg66 mice resided in nonhemopoietic stromal cells of the thymus. The phenotype is observed in mice heterozygous for the insertion and does not resemble any known mutations affecting thymic development. Preliminary studies in mice homozygous for transgene insertion reveal a more accelerated and pronounced phenotype suggesting a semidominant effect. The Tg66 mice may serve as a useful model to identify genes regulating thymic epithelial cell differentiation, thymic development, and function.},
  author       = {Assarsson, Erika and Chambers, Benedict J. and Hogstrand, Kari and Berntman, Emma and Lundmark, Carin and Fedorova, Ludmila and Imreh, Stefan and Grandien, Alf and Cardell, Susanna and Rozell, Bjorn and Ljunggren, Hans-Gustaf},
  issn         = {1550-6606},
  language     = {eng},
  number       = {8},
  pages        = {5018--5027},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Severe defect in thymic development in an insertional mutant mouse model},
  volume       = {178},
  year         = {2007},
}