共查询到20条相似文献,搜索用时 15 毫秒
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Uez N Lickert H Kohlhase J de Angelis MH Kühn R Wurst W Floss T 《Genesis (New York, N.Y. : 2000)》2008,46(9):463-477
Reciprocal signals from embryonic and extra-embryonic tissues pattern the embryo in proximal-distal (PD) and anterior-posterior (AP) fashion. Here we have analyzed three gene trap mutations of Sall4, of which one (Sall4-1a) led to a hypomorphic and recessive phenotype, demonstrating that Sall4-1a has yet undescribed extra-embryonic and embryonic functions in regulating PD and AP axis formation. In Sall4-1a mutants the self-maintaining autoregulatory interaction between Bmp4, Nodal and Wnt, which determines the PD axis was disrupted because of defects in the extra-embryonic visceral endoderm. More severely, two distinct Sall4 gene-trap mutants (Sall4-1a,b), resembling null mutants, failed to initiate Bmp4 expression in the extra-embryonic ectoderm and Nodal in the epiblast and were therefore unable to initiate PD axis formation. Tetraploid rescue underlined the extra-embryonic nature of the Sall4-1a phenotype and revealed a further embryonic function in Wnt/beta-catenin signaling to elongate the AP axis during gastrulation. This observation was supported through genetic interaction with beta-catenin mutants, since compound heterozygous mutants recapitulated the defects of Wnt3a mutants in posterior development. 相似文献
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Functional loss of p53 and ErbB2 overexpression are the frequent genetic alterations in human breast carcinomas. Here, we found that ErbB2 expression was upregulated in primary cultured mammary epithelial cells (MECs) isolated from mice with a defect in exons 5 and 6 of the p53 gene (p53(Delta5,6)). The reporter gene activity in the p53(Delta5,6) MECs transfected with the -756bp flanking region of the hErbB2 gene was higher than the wild type MECs. p53 inactivation selectively increased the level of AP-2alpha, but not AP-2beta and AP-2gamma and a mutation of the two AP-2 binding sites completely inhibited the reporter activity. 相似文献
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Placental vascularisation requires the AP-1 component fra1 总被引:11,自引:0,他引:11
Schreiber M Wang ZQ Jochum W Fetka I Elliott C Wagner EF 《Development (Cambridge, England)》2000,127(22):4937-4948
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Analysis of the mechanism of action of non-deletion hereditary persistence of fetal hemoglobin mutants in transgenic mice
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Transgenic mice carrying an (A)gamma gene construct containing a -382 5' truncation of the (A)gamma gene promoter have a phenotype of hereditary persistence of fetal hemoglobin (HPFH) but, when the CACCC box of the -382(A)gamma promoter is deleted, there is no gamma gene expression in the adult mice. We used this system to investigate the mechanism whereby human HPFH mutations result in gamma gene expression in the adult. Introduction of the -198 T-->C HPFH mutation into the CACCC-less (A)gamma gene construct re-established the HPFH phenotype, indicating that this mutation increases promoter strength, most probably by establishing a novel CACCC box sequence in the -198(A)gamma region. The HPFH phenotype was also re-established when the -117 C-->T HPFH mutation was introduced into a -141(A)gamma promoter with a destroyed CACCC box, indicating that this mutation increases gamma promoter strength in the absence of the CACCC motif. The T-->A -175 HPFH mutation failed to re-establish the HPFH phenotype when the CACCC box was deleted, indicating that gamma gene expression in this mutation is CACCC box dependent. These results provide the first in vivo experimental evidence in support of mechanistic heterogeneity of the non-deletion HPFH mutants. 相似文献
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Srinivasan S Bolick DT Hatley ME Natarajan R Reilly KB Yeh M Chrestensen C Sturgill TW Hedrick CC 《The Journal of biological chemistry》2004,279(30):31930-31936