Targeted disruption of the MHC class II <i>Aa</i> gene in C57BL/6 mice

Köntgen, Frank; Süss, Gabriele; Stewart, Colin L.; Steinmetz, Michael; Bluethmann, Horst

doi:10.1093/intimm/5.8.957

Cited by 366 publications

(276 citation statements)

References 25 publications

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“…Table 1 summarizes the data obtained at Ozgene with 216 gene‐targeted clones from parental ES cell line Bruce4 (background C57BL/6‐Thy1.1, +/+, and a/a) (Köntgen et al ., 1993) representing 115 different alleles. A total of 6,960 transferred blastocysts produced 943 male chimeras that were set up for breeding for at least 6 weeks and sired 3,518 black pups.…”

Section: Resultsmentioning

confidence: 99%

“…Gene targeting was carried out in the parental ES cell line Bruce4 (C57BL/6‐Thy1.1 background) (Köntgen et al ., 1993) with G418 selection; a gene‐targeted ES clone was injected into F2 of BALB/c x albino‐agouti C57BL/6 ( Tyr c / Tyr c and A/A) blastocysts; and GLT was obtained by crossing chimeras with C57BL/6 mice carrying a ROSA26‐Flp mutation in order to excise the FRT ‐flanked neomycin selectable marker gene. The floxed Tsc22d3 mutation devoid of the neomycin selectable marker gene was further maintained in a C57BL/6 background; this is the C57BL/6 strain used in the second and third configurations of Table 1.…”

Section: Methodsmentioning

confidence: 99%

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Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

Köentgen¹,

Lin

Κατίδου

et al. 2016

Genesis

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SummaryGene targeting in embryonic stem (ES) cells remains best practice for introducing complex mutations into the mouse germline. One aspect in this multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency of germline transmission: the transmission of the ES cell‐derived genome through the germline of chimeras to their offspring. A method whereby male chimeras transmit exclusively the genome of the injected ES cells to their offspring has been developed. The new technology, referred to as goGermline, entails injecting ES cells into blastocysts produced by superovulated homozygous Tsc22d3 floxed females mated with homozygous ROSA26‐Cre males. This cross produces males that are sterile due to a complete cell‐autonomous defect in spermatogenesis. The resulting male chimeras can be sterile but when fertile, they transmit the ES cell‐derived genome to 100% of their offspring. The method was validated extensively and in two laboratories for gene‐targeted ES clones that were derived from the commonly used parental ES cell lines Bruce4, E14, and JM8A3. The complete elimination of the collateral birth of undesired, non‐ES cell‐derived offspring in goGermline technology fulfills the reduction imperative of the 3R principle of humane experimental technique with animals. genesis 54:326–333, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

Köentgen¹,

Lin

Κατίδου

et al. 2016

Genesis

View full text Add to dashboard Cite

show abstract

“…4, further details available upon request). Linearized vector was electroporated into the Bruce4 ES cell line of C57BL/6J origin (20). Correctly targeted ES cell clones were identified by Southern blotting and injected into C57BL/6J Tyr c-2J/c-2J blastocysts.…”

Section: Generation Of Ptpn3-deficient Micementioning

confidence: 99%

Normal TCR Signal Transduction in Mice That Lack Catalytically Active PTPN3 Protein Tyrosine Phosphatase

Bauler¹,

Hughes

Arimura

et al. 2007

The Journal of Immunology

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PTPN3 (PTPH1) is a cytoskeletal protein tyrosine phosphatase that has been implicated as a negative regulator of early TCR signal transduction and T cell activation. To determine whether PTPN3 functions as a physiological negative regulator of TCR signaling in primary T cells, we generated gene-trapped and gene-targeted mouse strains that lack expression of catalytically active PTPN3. PTPN3 phosphatase-negative mice were born in expected Mendelian ratios and exhibited normal growth and development. Furthermore, numbers and ratios of T cells in primary and secondary lymphoid organs were unaffected by the PTPN3 mutations and there were no signs of spontaneous T cell activation in the mutant mice with increasing age. TCR-induced signal transduction, cytokine production, and proliferation was normal in PTPN3 phosphatase-negative mice. This was observed using both quiescent T cells and recently stimulated T cells where expression of PTPN3 is substantially up-regulated. We conclude, therefore, that the phosphatase activity of PTPN3 is dispensable for negative regulation of TCR signal transduction and T cell activation.

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“…Tg mice and littermate controls were sexmatched, over 8 wk old and housed under conventional conditions. CIITA and H2-Aa knockout mice backcrossed onto a C57B6/J background were provided by C. H. Chang and H. Bluethmann [25,29]. CIITA-p(III+IV) mice were on a mixed Sv129 Â C57BL/6 background [19].…”

Section: Micementioning

confidence: 99%

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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CIITA is a master regulatory factor for the expression of MHC class II (MHC-II) and accessory genes involved in Ag presentation. It has recently been suggested that CIITA also regulates numerous other genes having diverse functions within and outside the immune system. To determine whether these genes are indeed relevant targets of CIITA in vivo, we studied their expression in CIITA-transgenic and CIITA-deficient mice. In contrast to the decisive control of MHC-II and related genes by CIITA, nine putative non-MHC target genes (Eif3s2, Kpna6, Tap1, Yars, Col1a2, Ctse, Ptprr, Tnfsf6 and Plxna1) were found to be CIITA independent in all cell types examined. Two other target genes, encoding IL-4 and IFN-c, were indeed found to be up-and down-regulated, respectively, in CIITA-transgenic CD4 + T cells. However, there was no correlation between MHC-II expression and this Th2 bias at the level of individual transgenic T cells, indicating an indirect control by CIITA. These results show that MHC-II-restricted Ag presentation, and its indirect influences on T cells, remains the only pathway under direct control by CIITA in vivo. They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance.

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Targeted disruption of the MHC class II Aa gene in C57BL/6 mice

Cited by 366 publications

References 25 publications

Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

Normal TCR Signal Transduction in Mice That Lack Catalytically Active PTPN3 Protein Tyrosine Phosphatase

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

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