scholarly journals Strain-Dependent Modifier Genes Determine Survival in Zfp423 Mice

2020 ◽  
Vol 10 (11) ◽  
pp. 4241-4247
Author(s):  
Wendy A. Alcaraz ◽  
Zheng Liu ◽  
Phoebe Valdes ◽  
Edward Chen ◽  
Alan G. Valdovino Gonzalez ◽  
...  
Keyword(s):  
Survival Data ◽  
Regulatory Protein ◽  
Cerebellar Vermis ◽  
Chromosome 5 ◽  
Developmental Abnormalities ◽  
Modifier Locus ◽  
Transcriptional Regulatory ◽  
Aggregate Effect ◽  
Human Ortholog ◽  
Strain Dependent

Zfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse Zfp423 or its human ortholog ZNF423 are associated with a range of developmental abnormalities reminiscent of ciliopathies, including cerebellar vermis hypoplasia and other midline brain defects. Null mice have reduced viability in most strain backgrounds. Here we show complete lethality on a C57BL/6J background, dominant rescue in backcrosses to any of 13 partner strains, with strain-dependent survival frequencies, and evidence for a BALB/c-derived survival modifier locus on chromosome 5. Survival data indicate both perinatal and postnatal periods of lethality. Anatomical data from a hypomorphic gene trap allele observed on both C57BL/6J and BALB/c congenic backgrounds shows an aggregate effect of background on sensitivity to Zfp423 loss rather than a binary effect on viability.

scholarly journals Strain-dependent modifier genes determine survival in Zfp423 mice

2020 ◽  
Author(s):  
Wendy A. Alcaraz ◽  
Zheng Liu ◽  
Phoebe Valdes ◽  
Edward Chen ◽  
Alan G. Valdovino Gonzalez ◽  
...  
Keyword(s):  
Survival Data ◽  
Regulatory Protein ◽  
Cerebellar Vermis ◽  
Chromosome 5 ◽  
Developmental Abnormalities ◽  
Modifier Locus ◽  
Transcriptional Regulatory ◽  
Aggregate Effect ◽  
Human Ortholog ◽  
Strain Dependent

ABSTRACTZfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse Zfp423 or its human ortholog ZNF423 are associated with a range of developmental abnormalities reminiscent of ciliopathies, including cerebellar vermis hypoplasia and other midline brain defects. Null mice have reduced viability in most strain backgrounds. Here we show complete lethality on a C57BL/6J background, dominant rescue in backcrosses to any of 13 partner strains, with strain-dependent survival frequencies, and evidence for a BALB/c-derived survival modifier locus on chromosome 5. Survival data indicate both perinatal and postnatal periods of lethality. Anatomical data from a hypomorphic gene trap allele observed on both C57BL/6J and BALB/c congenic backgrounds shows an aggregate effect of background on sensitivity to Zfp423 loss rather than a binary effect on viability.

Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 23-30 ◽  
Author(s):  
J. Wallin ◽  
H. Eibel ◽  
A. Neubuser ◽  
J. Wilting ◽  
H. Koseki ◽  
...  
Keyword(s):  
T Cell ◽  
Regulatory Protein ◽  
Cell Maturation ◽  
Thymic Epithelial Cells ◽  
Total Size ◽  
Thymic Development ◽  
Transcriptional Regulatory ◽  
Thymus Cells ◽  
T Cell Maturation ◽  
Third Pharyngeal Pouch

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.

scholarly journals Phasin interactome reveals the interplay of PhaF with the polyhydroxyalkanoate transcriptional regulatory protein PhaD in Pseudomonas putida

2020 ◽  
Vol 22 (9) ◽  
pp. 3922-3936 ◽  
Author(s):  
Natalia A. Tarazona ◽  
Ana M. Hernández‐Arriaga ◽  
Ryan Kniewel ◽  
M. Auxiliadora Prieto
Keyword(s):  
Pseudomonas Putida ◽  
Regulatory Protein ◽  
Transcriptional Regulatory

Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment

2020 ◽  
Author(s):  
Xiantu Ou ◽  
Weibiao Lv
Keyword(s):  
Tumor Microenvironment ◽  
Regulatory Protein ◽  
Tumor Hypoxia ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Inflammatory Factors ◽  
Tumor Escape ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Transcriptional Regulatory

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.

scholarly journals Post-translational control of the MEF2A transcriptional regulatory protein

1999 ◽  
Vol 27 (13) ◽  
pp. 2646-2654 ◽  
Author(s):  
O. I. Ornatsky ◽  
D. M. Cox ◽  
P. Tangirala ◽  
J. J. Andreucci ◽  
Z. A. Quinn ◽  
...  
Keyword(s):  
Translational Control ◽  
Regulatory Protein ◽  
Transcriptional Regulatory

scholarly journals MtrR Modulates rpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae

2008 ◽  
Vol 191 (1) ◽  
pp. 287-297 ◽  
Author(s):  
Jason P. Folster ◽  
Paul J. T. Johnson ◽  
Lydgia Jackson ◽  
Vijaya Dhulipali ◽  
David W. Dyer ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Efflux Pump ◽  
Regulatory Protein ◽  
Multidrug Efflux ◽  
Binding Studies ◽  
Multidrug Efflux Pump ◽  
Pump System ◽  
Transcriptional Regulatory ◽  
Whole Genome Microarray ◽  
Dna Binding Studies

ABSTRACT The MtrR transcriptional-regulatory protein is known to repress transcription of the mtrCDE operon, which encodes a multidrug efflux pump possessed by Neisseria gonorrhoeae that is important in the ability of gonococci to resist certain hydrophobic antibiotics, detergents, dyes, and host-derived antimicrobials. In order to determine whether MtrR can exert regulatory action on other gonococcal genes, we performed a whole-genome microarray analysis using total RNA extracted from actively growing broth cultures of isogenic MtrR-positive and MtrR-negative gonococci. We determined that, at a minimum, 69 genes are directly or indirectly subject to MtrR control, with 47 being MtrR repressed and 22 being MtrR activated. rpoH, which encodes the general stress response sigma factor RpoH (sigma 32), was found by DNA-binding studies to be directly repressed by MtrR, as it was found to bind to a DNA sequence upstream of rpoH that included sites within the rpoH promoter. MtrR also repressed the expression of certain RpoH-regulated genes, but this regulation was likely indirect and a reflection of MtrR control of rpoH expression. Inducible expression of MtrR was found to repress rpoH expression and to increase gonococcal susceptibility to hydrogen peroxide (H2O2) and an antibiotic (erythromycin) recognized by the MtrC-MtrD-MtrE efflux pump system. We propose that, apart from its ability to control the expression of the mtrCDE-encoded efflux pump operon and, as a consequence, levels of gonococcal resistance to host antimicrobials (e.g., antimicrobial peptides) recognized by the efflux pump, the ability of MtrR to regulate the expression levels of rpoH and RpoH-regulated genes also modulates levels of gonococcal susceptibility to H2O2.

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