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Gene Review

Gt(ROSA)26Sor  -  gene trap ROSA 26, Philippe Soriano

Mus musculus

Synonyms: AV258896, Gtrgeo26, Gtrosa26, R26, ROSA26, ...
 
 
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Disease relevance of Gt(ROSA)26Sor

  • We analyzed eight K562 erythroleukemia cell clones, each carrying a single integrated copy of an mMT-I/beta-geo construct, using a system that can independently assess the level of beta-geo expression and the rate at which it is silenced [1].
  • Adenomas were composed of proliferating beta-Gal-positive and -negative epithelial cells, suggesting that they arose through cooperative interactions between 129/Sv(Id-1) and B6 ROSA26/+ cells [2].
  • METHODS: Adenovirus expressing Cre-recombinase (Adeno-Cre) was intraductally injected into the prostate of ROSA26 reporter mice [3].
  • ES cells were infected with U3 beta geo, a U3 gene trap retrovirus that contains coding sequences for a beta-galactosidase-neomycin phosphotransferase hybrid protein [4].
  • METHODS: Myocardial infarction was induced cryogenically in backcrossed ROSA 26 transgenic x C57BL/6J mice (n = 75) [5].
 

High impact information on Gt(ROSA)26Sor

  • An Flp indicator mouse expressing alkaline phosphatase from the ROSA26 locus [6].
  • When control chimeric mice made of wild-type cells and ROSA26 cells (i.e., both carrying intact Agtr1a) were infused with Ang II, fibroblast proliferation was found equally in these cardiomyocyte types [7].
  • The distribution of ROSA26 cardiomyocytes overlaps completely with that of Ang II binding, indicating that the majority of Ang II receptors reside on cardiomyocytes [7].
  • To determine whether AAV-mediated gene targeting can occur in vivo, we developed a mouse model that contains a mutant, nuclear-localized lacZ gene inserted at the ubiquitously expressed ROSA26 locus [8].
  • To confirm the cells' bone marrow origin, chimeric mice were created by the rescue of irradiated C57BL/6 mice with marrow from ROSA26, a congenic line expressing lacZ [9].
 

Chemical compound and disease context of Gt(ROSA)26Sor

  • Using recombinant adenoviruses expressing a functional Cre (ADV-Cre) and ROSA26 reporter mice, we show here that ADV-Cre infused intraluminally in a small volume (10 microl) conditionally excises the loxP site, resulting in lacZ expression in uterine luminal epithelial cells without significantly affecting pregnancy [10].
 

Biological context of Gt(ROSA)26Sor

  • A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre-recombinase (SM-Cre-ER(T2)) transgene and a stop-floxed beta-galactosidase gene in the Rosa26 locus: the SM-CreER(T2)(ki)/rosa26 mouse [11].
  • Staining of ROSA26 tissues and fluorescence-activated cell sorter-Gal analysis of hematopoietic cells demonstrates ubiquitous expression of the proviral beta geo reporter gene, and bone marrow transfer experiments illustrate the general utility of this strain for chimera and transplantation studies [12].
  • By mating the reporter strain with Cre-expressing transgenic mice, we have shown that the loxP-flanked ROSA26 allele is accessible to Cre during early embryogenesis, as well as in a specific hematopoietic lineage (T lymphocytes) [13].
  • The beta-galactosidase-neomycin phosphotransferase fusion gene (betageo)-trapped ROSA26 locus was modified by gene targeting such that betageo is expressed only after Cre-mediated excision of loxP-flanked DNA sequences. betageo from the excised ROSA26 allele is expressed ubiquitously in embryos and adult mice [13].
  • Finally, when injected directly into the renal parenchyma, shortly after ischemic/reperfusion injury, renal Sca-1(+)Lin(-) cells, derived from ROSA26 reporter mice, adopt a tubular phenotype and potentially could contribute to kidney repair [14].
 

Anatomical context of Gt(ROSA)26Sor

  • The ROSA beta geo26 (ROSA26) mouse strain was produced by random retroviral gene trapping in embryonic stem cells [12].
  • Using a PLP-CreERT2 transgene, we have generated mice that show specific inducible Cre function, as analyzed by cross-breeding experiments into the Rosa26 Cre-LacZ reporter line, in developing and adult Schwann cells, in mature myelinating oligodendrocytes, and in undifferentiated NG2-positive oligodendrocyte precursors in the adult [15].
  • The zygotic expression of the beta-geo transgene in the ROSA26 mouse strain could be inhibited until at least the early blastula stages [16].
  • In nude mice transplanted with fetal liver cells from (ROSA26 x CD4C/N1(EC)) F(1) Tg mice, abnormal vessels were of recipient origin [17].
  • We established an ES cell line in which exogenous pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus [18].
 

Associations of Gt(ROSA)26Sor with chemical compounds

  • However, ENU-treated B6 mice carrying both Apc(Min) and ROSA26 are resistant to mammary tumor formation [19].
  • When such mice were crossed with the ROSA-26 or Z/EG reporter mice, neural stem cells were permanently labeled after administration of tamoxifen [20].
  • Crossing SERT-cre mice with the ROSA26-stop-lacZ or ROSA26-stop-YFP reporter mice similarly revealed a near perfect correlation between staining for serotonin-synthetic enzyme tryptophan hydroxylase and beta-galactosidase or YFP [21].
  • To characterize the mode of action of angiotensin II (Ang II) in cardiac remodeling, we generated chimeric mice that are made of both homozygous Ang II receptor type 1A gene (Agtr1a) null mutant cells and Agtr1a intact cells expressing the lacZ gene (ROSA26) [7].
  • ROSA 26 marrow mononuclear cells (containing the beta-geo transgene that encodes beta-galactosidase and neomycin resistance activities) were cultured in the presence of macrophage colony-stimulating factor and flt3 Ligand for 6 days to generate monocytic cells at all stages of maturation [22].
 

Regulatory relationships of Gt(ROSA)26Sor

  • We have targeted a K-ras allele in mouse embryonic stem (ES) cells to express a K-Ras(V12) oncoprotein along with a marker protein (beta-geo) from a single bicistronic transcript [23].
  • Chimeric mice were made between wild-type ROSA26 transgenic mouse embryos (whose cells express beta-galactosidase) and Unc5h3 mutant embryos [24].
  • METHODS AND RESULTS: Inferior vena cava-to-carotid artery interposition grafting between C57Bl/6 and congenic beta-galactosidase-expressing ROSA26 mice was performed [25].
  • Here, we show a detailed in situ analysis of a mouse strain with a trapped Spred-2 gene, bringing a beta-galactosidase and neomycin fusion gene (beta-geo) under the control of the endogenous Spred-2 promoter [26].
 

Other interactions of Gt(ROSA)26Sor

  • Thus, ROSA26 mice carry a modifier of Min-induced mammary tumor susceptibility [19].
  • In order to test the excision activity and tissue distribution of the Cre recombinase, the Tie2-Cre transgenic line was crossed with the mouse strain carrying the Smad4 conditional alleles (Smad4(Co/Co)) or the reporter line ROSA26 [27].
  • In chimeras derived from Hand1-null ES cells and ROSA26 embryos, mutant cells were underrepresented in the left caudal region of the linear heart tube at E8 [28].
  • Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice [29].
  • In order to test the excision activity of the Cre recombinase, the Col10a1-Cre transgenic line was crossed with the mouse strain carrying the Smad4 conditional alleles (Smad4co/co) and the reporter line ROSA26 [30].
 

Analytical, diagnostic and therapeutic context of Gt(ROSA)26Sor

  • METHODS: The beta-gal activity and GFP were examined in the hematopoietic cells of ROSA26 and GFP transgenic mice, respectively, by flow cytometry [31].
  • When wild-type E12 mouse kidneys were grafted into anterior chambers of ROSA26 mice, in which the beta-galactosidase transgene is expressed ubiquitously, glomerular and microvascular endothelial cells stemmed from the graft, even after maintenance of kidneys in organ culture for 6 days before grafting [32].
  • Electroporation of a construct encoding a Cre-enhanced green fluorescent protein (EGFP) fusion protein into explants from ROSA26 reporter animals resulted in extensive activation of beta-galactosidase expression, indicating that the electroporated construct produced functionally active protein [33].
  • We have used freshly isolated side population cells derived from ROSA26 adult bone marrow and demonstrate that despite being unable to contribute to embryos following blastocyst injection, or air liquid interface cultures or denuded tracheal xenografts, they could contribute to the tracheal epithelium in vivo [34].
  • Adoptive transfer experiments, as well as studies involving lacZ-transgenic mice (ROSA-26) revealed that CTLs to viral antigens are sufficient to destroy virus-infected hepatocytes, indicating that CTLs to beta-gal can not solely account for the observed hepatocyte destruction that has characterized the use of first generation viruses [35].

References

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