The role of STAT transcription factors in apoptosis regulation of hypothalamic neurons in aging in HER-2/neu transgenic mice and wild-type FVB/N mice

2016 ◽  
Vol 468 (1) ◽  
pp. 217-219 ◽  
Author(s):  
E. D. Bazhanova ◽  
V. N. Anisimov
Keyword(s):  
Transcription Factors ◽  
Transgenic Mice ◽  
Wild Type ◽  
Hypothalamic Neurons ◽  
Her 2 ◽  
Apoptosis Regulation

scholarly journals Enteral arginase II provides ornithine for citrulline synthesis

2011 ◽  
Vol 300 (1) ◽  
pp. E188-E194 ◽  
Author(s):  
Juan C. Marini ◽  
Bettina Keller ◽  
Inka Cajo Didelija ◽  
Leticia Castillo ◽  
Brendan Lee
Keyword(s):  
Small Intestine ◽  
Stable Isotope ◽  
Transgenic Mice ◽  
Small Intestinal Mucosa ◽  
Wild Type ◽  
Proline Utilization ◽  
Small Intestinal ◽  
Arginase Ii ◽  
Citrulline Synthesis

The synthesis of citrulline from arginine in the small intestine depends on the provision of ornithine. To test the hypothesis that arginase II plays a central role in the supply of ornithine for citrulline synthesis, the contribution of dietary arginine, glutamine, and proline was determined by utilizing multitracer stable isotope protocols in arginase II knockout (AII−/−) and wild-type (WT) mice. The lack of arginase II resulted in a lower citrulline rate of appearance (121 vs. 137 μmol·kg−1·h−1) due to a reduced availability of ornithine; ornithine supplementation was able to restore the rate of citrulline production in AII−/− to levels comparable with WT mice. There were significant differences in the utilization of dietary citrulline precursors. The contribution of dietary arginine to the synthesis of citrulline was reduced from 45 to 10 μmol·kg−1·h−1 due to the lack of arginase II. No enteral utilization of arginine was observed in AII−/− mice (WT = 25 μmol·kg−1·h−1), and the contribution of dietary arginine through plasma ornithine was reduced in the transgenic mice (20 vs. 13 μmol·kg−1·h−1). Dietary glutamine and proline utilization were greater in AII−/− than in WT mice (20 vs. 13 and 1.4 vs. 3.7 μmol·kg−1·h−1, respectively). Most of the contribution of glutamine and proline was enteral rather than through plasma ornithine. The arginase isoform present in the small intestinal mucosa has the role of providing ornithine for citrulline synthesis. The lack of arginase II results in a greater contribution of plasma ornithine and dietary glutamine and proline to the synthesis of citrulline.

scholarly journals Essential Role of Phospholipase Cγ2 in Early B-Cell Development and Myc-Mediated Lymphomagenesis

2006 ◽  
Vol 26 (24) ◽  
pp. 9364-9376 ◽  
Author(s):  
Renren Wen ◽  
Yuhong Chen ◽  
Li Bai ◽  
Guoping Fu ◽  
James Schuman ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Cell Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Cell Receptor ◽  
Wild Type ◽  
Interleukin 7

ABSTRACT Phospholipase Cγ2 (PLCγ2) is a critical signaling effector of the B-cell receptor (BCR). Here we show that PLCγ2 deficiency impedes early B-cell development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B cells. PLCγ2 deficiency impairs pre-BCR-mediated functions, leading to enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the selected large pre-B cells. Consequently, PLCγ2 deficiency renders large pre-B cells susceptible to transformation, resulting in dramatic acceleration of Myc-induced lymphomagenesis. PLCγ2 −/− Eμ-Myc transgenic mice mainly develop lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are uncommon in wild-type Eμ-Myc transgenics. Furthermore, lymphomas from PLCγ2 −/− Eμ-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed alterations in Arf or p53. Thus, PLCγ2 plays an important role in pre-BCR-mediated early B-cell development, and its deficiency leads to markedly increased pools of the most at-risk large pre-B cells, which display hyperresponsiveness to IL-7 and express high levels of RAGs, making them prone to secondary mutations and Myc-induced malignancy.

scholarly journals Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Chiara Berteotti ◽  
Viviana Lo Martire ◽  
Sara Alvente ◽  
Stefano Bastianini ◽  
Cristiano Bombardi ◽  
...  
Keyword(s):  
Histidine Decarboxylase ◽  
Neuron Development ◽  
Wild Type ◽  
Hypothalamic Neurons ◽  
Neuron Number ◽  
Knock Out ◽  
Orexin Neuron ◽  
Knock Out Mice ◽  
Deficient Mice

The loss of hypothalamic neurons that produce wake-promoting orexin (hypocretin) neuropeptides is responsible for narcolepsy type 1 (NT1). While the number of histamine neurons is increased in patients with NT1, results on orexin-deficient mouse models of NT1 are inconsistent. On the other hand, the effect of histamine deficiency on orexin neuron number has never been tested on mammals, even though histamine has been reported to be essential for the development of a functional orexin system in zebrafish. The aim of this study was to test whether histamine neurons are increased in number in orexin-deficient mice and whether orexin neurons are decreased in number in histamine-deficient mice. The hypothalamic neurons expressing L-histidine decarboxylase (HDC), the histamine synthesis enzyme, and those expressing orexin A were counted in four orexin knock-out mice, four histamine-deficient HDC knock-out mice, and four wild-type C57BL/6J mice. The number of HDC-positive neurons was significantly higher in orexin knock-out than in wild-type mice (2,502 ± 77 vs. 1,800 ± 213, respectively, one-tailed t-test, P = 0.011). Conversely, the number of orexin neurons was not significantly lower in HDC knock-out than in wild-type mice (2,306 ± 56 vs. 2,320 ± 120, respectively, one-tailed t-test, P = 0.459). These data support the view that orexin peptide deficiency is sufficient to increase histamine neuron number, supporting the involvement of the histamine waking system in the pathophysiology of NT1. Conversely, these data do not support a significant role of histamine in orexin neuron development in mammals.

scholarly journals THE ROLE OF TRANSCRIPTION FACTORS DFOXO, DSIR2 AND HSP70 IN LIFESPAN ALTERATION OF DROSOPHILA MELANOGASTER IN DIFFERENT LIGHT CONDITIONS

2010 ◽  
Vol 8 (3) ◽  
pp. 67-80 ◽  
Author(s):  
Aleksey A Moskalev ◽  
Olga A Malysheva
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Stress Response ◽  
Life Span ◽  
Light Regime ◽  
Light Conditions ◽  
Wild Type ◽  
Stress Response Genes ◽  
Significant Difference

It was investigated the role of stress-response genes (dFOXO, dSir2, Hsp70) in regulation of life span of Drosophila in response to light regime alteration. It was revealed the FOXO-dependant mechanism of lifespan increasing at darkness conditions. The distance of lifespan of FOXO homozygous mutants at different light conditions were absent 3 times from 4 times. It was shown, that homozygotes with deletion of dSir2 have more significant difference between lifespan at standard light and darkness conditions with comparing to wild type and heterozygous strain. The same tendency was also detected the in the strains with Hsp70 deletions. It was produced the evidences of two mechanisms of light regime influence on lifespan: metabolism intensification at light conditions and neuroendocrine-determinated lifespan increasing at darkness conditions.

scholarly journals Activation of endothelial intrinsic NF-κB pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2521-2529 ◽  
Author(s):  
Dongmei Song ◽  
Xiaobing Ye ◽  
Honglei Xu ◽  
Shu Fang Liu
Keyword(s):  
Transgenic Mice ◽  
Tissue Factor ◽  
Protein C ◽  
Nuclear Factor Κb ◽  
Tissue Factor Expression ◽  
Wild Type ◽  
Endothelial Protein C Receptor ◽  
Lps Challenge ◽  
Factor Expression

Abstract Although the role of systemic activation of the nuclear factor κB (NF-κB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-κB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant I-κBα, an inhibitor of NF-κB, selectively on endothelium, and their wild-type littermates to define the role of endothelial-specific NF-κB in septic coagulation. In wild-type mice, lipopolysaccharide (LPS) challenge (5 mg/kg intraperitoneally) caused markedly increased plasma markers of coagulation, decreased plasma fibrinogen level, and widespread tissue fibrin deposition, which were abrogated by endothelial NF-κB blockade in transgenic mice. Endothelial NF-κB blockade inhibited tissue factor expression in endothelial cells, but not in leukocytes. Endothelial NF-κB blockade did not inhibit LPS-induced tissue factor expression in heart, kidney, and liver. Endothelial NF-κB blockade prevented LPS down-regulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited tissue tumor necrosis factor-α converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level. Our data demonstrate that endothelial intrinsic NF-κB signaling plays a pivotal role in septic coagulation and suggests a link between endothelial-specific NF-κB activation and the impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.

scholarly journals Critical Role of Egr Transcription Factors in Regulating Insulin Biosynthesis, Blood Glucose Homeostasis, and Islet Size

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3040-3053 ◽  
Author(s):  
Isabelle Müller ◽  
Oliver G. Rössler ◽  
Christine Wittig ◽  
Michael D. Menger ◽  
Gerald Thiel
Keyword(s):  
Transcription Factors ◽  
Glucose Tolerance ◽  
Transgenic Mice ◽  
Glucose Homeostasis ◽  
Insulin Biosynthesis ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Islet Size

Expression of early growth response protein (Egr)-1, a protein of the Egr family of zinc finger transcription factors, is stimulated in glucose-treated pancreatic β-cells and insulinoma cells. The purpose of this study was to elucidate the role of Egr transcription factors in pancreatic β-cells in vivo. To overcome the problem associated with redundancy of functions between Egr proteins, conditional transgenic mice were generated expressing a dominant-negative mutant of Egr-1 in pancreatic β-cells. The Egr-1 mutant interferes with DNA binding of all Egr proteins and thus impairs the biological functions of the entire Egr family. Expression of the Egr-1 mutant reduced expression of TGFβ and basic fibroblast growth factor, known target genes of Egr-1, whereas the expression of Egr-1, Egr-3, Ets-like gene-1 (Elk-1), and specificity protein-3 was not changed in the presence of the Egr-1 mutant. Expression of the homeobox protein pancreas duodenum homeobox-1, a major regulator of insulin biosynthesis, was reduced in islets expressing the Egr-1 mutant. Accordingly, insulin mRNA and protein levels were reduced by 75 or 25%, respectively, whereas expression of glucagon and somatostatin was not altered after expression of the Egr-1 mutant in β-cells. Glucose tolerance tests revealed that transgenic mice expressing the Egr-1 mutant in pancreatic β-cells displayed impaired glucose tolerance. In addition, increased caspase-3/7 activity was detected as a result of transgene expression, leading to a 20% decrease of the size of the islets. These results show that Egr proteins play an important role in controlling insulin biosynthesis, glucose homeostasis, and islet size of pancreatic β-cells in vivo.

scholarly journals Selection for Loss of p53 Function in T-Cell Lymphomagenesis Is Alleviated by Moloney Murine Leukemia Virus Infection in myc Transgenic Mice

2001 ◽  
Vol 75 (20) ◽  
pp. 9790-9798 ◽  
Author(s):  
Euan W. Baxter ◽  
Karen Blyth ◽  
Ewan R. Cameron ◽  
James C. Neil
Keyword(s):  
Transgenic Mice ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Tumor Cell Lines ◽  
Wild Type ◽  
Allele Loss ◽  
Selection For

ABSTRACT Thymic lymphomas induced by Moloney murine leukemia virus (MMLV) have provided many examples of oncogene activation, but the role of tumor suppressor pathways in these tumors is less clear. These tumors display little evidence of loss of heterozygosity, and MMLV is only weakly synergistic with the Trp53 null genotype, suggesting that viral lymphomagenesis involves mechanisms which do not require mutational loss of Trp53function. To explore this relationship in greater depth, we infected CD2-myc transgenic mice with MMLV and examined the role of Trp53 in the genesis of these tumors. Most (19 of 27) of the tumors from MMLV-infected, CD2-myc Trp53 +/− mice retained the wild-typeTrp53 allele in vivo while tumors of uninfected CD2-myc Trp53 +/− mice invariably showed allele loss from a significant fraction of primary tumor cells. The functional integrity of the Trp53gene in these tumors was indicated by ongoing allele loss or selection for mutational stabilization during in vitro propagation and by the radiosensitivity of selected Trp53 +/−tumor cell lines. An inverse correlation was noted between retention of the wild-type Trp53 allele and expression of p19ARF, providing further evidence of negative-feedback control of the latter by p53. However, expression of p19ARFdoes not appear to be counterselected in the absence of p53, and its integrity in Trp53 +/− tumors was indicated by its transcriptional upregulation on Trp53 wild-type allele loss in vitro in selected tumor cell lines. The role of MMLV was investigated further by analysis of proviral insertion sites in tumors of CD2-myc transgenic mice sorted forTrp53 genotype. A proportion of tumors showed insertions at Runx2, an oncogene which has been shown to collaborate independently with CD2-myc and with theTrp53 null genotype, and at a novel common integration site (ptl-1) on chromosome 8. Genotypic analysis of the panel of tumors suggested that neither of these integrations is functionally redundant with loss of p53, but it appears that the combination of the MMLV oncogenic program with the CD2-myc oncogene relegates p53 loss to a late step in tumor progression or in vitro culture. While the means by which these tumors preempt the p53 tumor suppressor response remains to be established, this study provides further evidence that irreversible inactivation of this pathway is not a prerequisite for tumor development in vivo.

scholarly journals Central Nervous System–Targeted Complement Inhibition Mediates Neuroprotection after Closed Head Injury in Transgenic Mice

2003 ◽  
Vol 23 (9) ◽  
pp. 1070-1074 ◽  
Author(s):  
Mario Rancan ◽  
Maria C. Morganti-Kossmann ◽  
Scott R. Barnum ◽  
Silvia Saft ◽  
Oliver I. Schmidt ◽  
...  
Keyword(s):  
Head Injury ◽  
Transgenic Mice ◽  
Closed Head Injury ◽  
Wild Type ◽  
Complement Inhibition ◽  
Future Studies ◽  
Closed Head ◽  
Targeted Expression ◽  
The Complement System

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood–brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.

Sign in / Sign up

Export Citation Format

Share Document