Modulation of the neuronal response to ischaemia by somatostatin analogues in wild-type and knock-out mouse retinas

Abstract Background Decreased eNOS activity is the hallmark of endothelial dysfunction and is associated with cardiovascular and renal disorders. Besides NO, endothelial cells produce numerous other small molecules, peptides, and proteins, which modulate the function of adjacent cells. For instance, neuregulin-1 (NRG-1) is an endothelium-derived growth factor, which plays crucial roles in cardiovascular development, has cardioprotective properties, and induces growth and differentiation of cell types in different organs, including the kidney. Purpose Although the cardioprotective effects of endothelium-derived NO and NRG-1 are well established, their interaction is not clear. Therefore, we studied the interaction between the NO/eNOS and NRG-1/ErbB signalling pathways in a transgenic eNOS knock-out mouse model (eNOS−/−) treated with subpressor doses of angiotensin II (AngII). Methods eNOS−/− mice and their wild type (WT) littermates (n=64, 15 weeks old) were randomized for implantation of osmotic minipumps with AngII (400 ng/kg.min) for 28 days or sham surgery. Mice were randomized to receive either daily NRG-1 injections (20 μg/kg, intraperitoneal) or vehicle for 4 weeks (n=8/group). Hypertrophy and fibrosis were measured in left ventricle (LV) and kidneys using echography and immunohistochemical staining. Results Although blood pressure was higher in eNOS−/− mice compared to their WT littermates, it was unaffected by a subpressor dose of AngII. Masson's trichrome staining showed that AngII significantly increased LV (interstitial and perivascular) and renal fibrosis in eNOS−/− mice, but not in WT controls (see figure for LV data). NRG-1 reversed this AngII-induced LV and renal fibrosis caused by eNOS deficiency. There was also significant hypertrophy of LV and kidneys in eNOS−/− mice treated with AngII, which was again normalized by NRG-1 treatment. Moreover, NRG-1 significantly attenuated albuminuria induced by eNOS deficiency under AngII treatment. Conclusions This study demonstrates that the anti-fibrotic and anti-hypertrophic effects of NRG-1 are independent from the NO/eNOS pathway in both heart and kidney. Strikingly, NRG-1 is able to compensate for some of the negative effects of eNOS deficiency, at least in conditions of AngII stimulation. Acknowledgement/Funding supported by university of Antwerp

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Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx-/-) and the 129sv wild type mouse

The Journal of Comparative Neurology ◽

10.1002/cne.23390 ◽

2013 ◽

pp. n/a-n/a

Author(s):

Louise Rovsing ◽

Martin Fredensborg Rath ◽

Morten Møller

Keyword(s):

Wild Type Mouse ◽

Wild Type ◽

Knock Out ◽

Neuronal Systems ◽

Knock Out Mouse

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Abstract P155: HSF-1 Deletion Induces MDR1 Gene in the Heart and Protects from Doxorubicin-Induced Cardiotoxicity

Circulation Research ◽

10.1161/res.109.suppl_1.ap155 ◽

2011 ◽

Vol 109 (suppl_1) ◽

Author(s):

Karthikeyan Krishnamurthy ◽

Lawrence Druhan ◽

Govindasamy Ilangovan

Keyword(s):

Cardiac Dysfunction ◽

Mdr1 Gene ◽

Heat Shock Factor 1 ◽

Wild Type ◽

Rt Pcr ◽

Glycoprotein P ◽

Knock Out ◽

P Glycoprotein ◽

Mdr1 Gene Expression ◽

Knock Out Mouse

Heat shock factor 1 (HSF-1) has been found to be a frontline responder of different stresses in eukaryotic cells. Deletion of HSF-1 has been reported to develop defects in mice. In the present work we report that deletion of HSF-1 induced multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) expression. Both RT-PCR and western blotting, confirmed the higher level of MDR1 gene expression and P-gp protein in HSF-1 knock out mouse hearts. P-gp is well known ATP binding cassette, which extrudes intracellular drugs upon binding ATP. Hence the phenotype of the P-gp pump in HSF-1 −/− mice was studied in the form of Doxorubicin (Dox) extrusion in the heart. Cardiomyocytes isolated from HSF-1 −/− and HSF-1 +/− mice retained very less intracellular Dox, compared to wild type counterparts. Similarly, both HSF-1 +/− and HSF-1 −/− mice were less susceptible for Dox-induced cardiotoxicity, as seen from reduced cardiac dysfunction in these group against Dox (as confirmed by cardiac MRI and echocardiography). Further confirmatory studies revealed that deletion of HSF-1 enhances NF-B, which subsequently induces MDR1 gene. These results reveal that inactivation of HSF-1 in the heart will be a potential approach to prevent Dox-induced cardiotoxicity.

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Functional characterization of the H+/K+ ATPase in wild type and gastrin knock-out mice

Zeitschrift für Gastroenterologie ◽

10.1055/s-2007-982721 ◽

2007 ◽

Vol 45 (05) ◽

Author(s):

A Schnur ◽

P Hegyi ◽

V Venglovecz ◽

Z Rakonczay ◽

I Ignáth ◽

...

Keyword(s):

Functional Characterization ◽

Wild Type ◽

Knock Out ◽

Knock Out Mice

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Faculty Opinions recommendation of Loss of cone function without degeneration in a novel Gnat2 knock-out mouse.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732844281.793543803 ◽

2018 ◽

Author(s):

Gordon Fain

Keyword(s):

Knock Out ◽

Cone Function ◽

Knock Out Mouse

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Brain immune cells characterization in UCMS exposed P2X7 knock-out mouse

Brain Behavior and Immunity ◽

10.1016/j.bbi.2021.02.012 ◽

2021 ◽

Vol 94 ◽

pp. 159-174

Author(s):

Romain Troubat ◽

Samuel Leman ◽

Katleen Pinchaud ◽

Alexandre Surget ◽

Pascal Barone ◽

...

Keyword(s):

Immune Cells ◽

Knock Out ◽

Knock Out Mouse

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Effects of cofD gene knock-out on the methanogenesis of Methanobrevibacter ruminantium

AMB Express ◽

10.1186/s13568-021-01236-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jian Ma ◽

Xueying Wang ◽

Ting Zhou ◽

Rui Hu ◽

Huawei Zou ◽

...

Keyword(s):

Growth Rate ◽

Specific Growth ◽

Production Capacity ◽

Maximum Amount ◽

Logarithmic Phase ◽

Wild Type ◽

Knock Out ◽

Maximum Biomass ◽

Reproductive Ability ◽

Methanobrevibacter Ruminantium

AbstractThis study aimed to investigate the effects of cofD gene knock-out on the synthesis of coenzyme F420 and production of methane in Methanobrevibacter ruminantium (M. ruminantium). The experiment successfully constructed a cofD gene knock-out M. ruminantium via homologous recombination technology. The results showed that the logarithmic phase of mutant M. ruminantium (12 h) was lower than the wild-type (24 h). The maximum biomass and specific growth rate of mutant M. ruminantium were significantly lower (P < 0.05) than those of wild-type, and the maximum biomass of mutant M. ruminantium was approximately half of the wild-type; meanwhile, the proliferation was reduced. The synthesis amount of coenzyme F420 of M. ruminantium was significantly decreased (P < 0.05) after the cofD gene knock-out. Moreover, the maximum amount of H2 consumed and CH4 produced by mutant were 14 and 2% of wild-type M. ruminantium respectively. In conclusion, cofD gene knock-out induced the decreased growth rate and reproductive ability of M. ruminantium. Subsequently, the synthesis of coenzyme F420 was decreased. Ultimately, the production capacity of CH4 in M. ruminantium was reduced. Our research provides evidence that cofD gene plays an indispensable role in the regulation of coenzyme F420 synthesis and CH4 production in M. ruminantium.

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