scholarly journals Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11β-HSD1 Deficient Mice

2016 ◽  
Vol 28 (1) ◽  
Author(s):  
J. Qiu ◽  
D. R. Dunbar ◽  
J. Noble ◽  
C. Cairns ◽  
R. Carter ◽  
...  
Keyword(s):  
Mrna Levels ◽  
Wild Type ◽  
Deficient Mice

Differential response to myocardial reperfusion injury in eNOS-deficient mice

2002 ◽  
Vol 282 (6) ◽  
pp. H2422-H2426 ◽  
Author(s):  
Brent R. Sharp ◽  
Steven P. Jones ◽  
David M. Rimmer ◽  
David J. Lefer
Keyword(s):  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
In Vivo Model ◽  
Pcr Analysis ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Wild Type ◽  
Significant Difference ◽  
Deficient Mice

Two strains of endothelial nitric oxide synthase (eNOS)-deficient (−/−) mice have been developed that respond differently to myocardial ischemia-reperfusion (MI/R). We evaluated both strains of eNOS−/− mice in an in vivo model of MI/R. Harvard (Har) eNOS−/− mice ( n = 12) experienced an 84% increase in myocardial necrosis compared with wild-type controls ( P < 0.05). University of North Carolina (UNC) eNOS−/−( n = 10) exhibited a 52% reduction in myocardial injury versus wild-type controls ( P < 0.05). PCR analysis of myocardial inducible NO synthase (iNOS) mRNA levels revealed a significant ( P < 0.05) increase in the UNC eNOS−/− mice compared with wild-type mice, and there was no significant difference between the Har eNOS−/− and wild-type mice. UNC eNOS−/− mice treated with an iNOS inhibitor (1400W) exacerbated the extent of myocardial necrosis. When treated with 1400W, Har eNOS−/− did not exhibit a significant increase in myocardial necrosis. These data demonstrate that two distinct strains of eNOS−/− mice display opposite responses to MI/R. Although the protection seen in the UNC eNOS−/− mouse may result from compensatory increases in iNOS, other genes may be involved.

scholarly journals Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice

2012 ◽  
Vol 303 (11) ◽  
pp. R1186-R1194 ◽  
Author(s):  
Thomas H. Reynolds ◽  
Erin Merrell ◽  
Nicholas Cinquino ◽  
Megan Gaugler ◽  
Lily Ng
Keyword(s):  
High Fat Diet ◽  
Insulin Action ◽  
Mrna Levels ◽  
Wild Type ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Akt Isoforms ◽  
Forkhead Box ◽  
Gene Ablation ◽  
Deficient Mice

The purpose of the present study was to determine the effect of Akt gene ablation on Akt/Forkhead Box O (FOXO) signaling and atrogene expression. This was accomplished by studying wild-type (WT) and isoform-specific Akt knockout (Akt1−/− and Akt2−/−) mice. The ability of insulin to promote Akt phosphorylation on Ser473 was significantly lower in extensor digitorum longus (EDL) and soleus muscles from Akt1−/− and Akt2−/− mice compared with WT mice. Total Akt1 protein levels were significantly lower in EDL muscles of Akt2−/− mice compared with WT mice, a process that appears to be posttranscriptionally regulated as Akt1 mRNA levels were unchanged. The loss of Akt1 protein in EDL muscles of Akt2−/− mice does not appear to be due to insulin resistance because 4 mo of a high-fat diet failed to reduce Akt1 protein levels in muscles of WT mice. Although FOXO3a phosphorylation and atrogin-1 expression were unaltered in muscles of Akt1−/− and Akt2−/− mice, the expression of the atrogenes Bnip3 and gabarapl were significantly elevated in muscles of both Akt1 and Akt2 knockout mice. Finally, the expression of striated activator of Rho signaling was significantly increased in muscles of Akt2−/− mice compared with Akt1−/− and WT mice. Our results demonstrate that the ablation of Akt isoforms disassociates insulin action and Akt/FOXO signaling to atrogenes.

Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPARα-dependent manner

2013 ◽  
Vol 305 (9) ◽  
pp. E1093-E1102 ◽  
Author(s):  
Andressa Bolsoni-Lopes ◽  
William T. Festuccia ◽  
Talita S. M. Farias ◽  
Patricia Chimin ◽  
Francisco L. Torres-Leal ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Palmitoleic Acid ◽  
Whole Body ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Wild Type ◽  
Acid Incorporation ◽  
Gene And Protein Expression ◽  
Fatty Acid Incorporation ◽  
Deficient Mice

We investigated whether palmitoleic acid, a fatty acid that enhances whole body glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from wild-type or PPARα-deficient mice treated with 16:1n7 (300 mg·kg−1·day−1) or oleic acid (18:1n9, 300 mg·kg−1·day−1) by gavage for 10 days were evaluated for lipolysis, TAG, and glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and pSer660-HSL. Such increase in lipolysis induced by 16:1n7, which can be prevented by pharmacological inhibition of PPARα, was associated with higher rates of PPARα binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0 increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose without affecting glyceroneogenesis and glycerokinase expression. Corroborating in vitro findings, treatment of wild-type but not PPARα-deficient mice with 16:1n7 increased primary adipocyte basal and stimulated lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7 treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose in both wild-type and PPARα-deficient mice. In conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a mechanism that requires a functional PPARα.

scholarly journals Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 195-206 ◽  
Author(s):  
Hiroshi Tsuneki ◽  
Takashi Nagata ◽  
Mikio Fujita ◽  
Kanta Kon ◽  
Naizhen Wu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Oral Intake ◽  
Mrna Levels ◽  
Active Period ◽  
Wild Type ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Deficient Mice

Abstract Nicotine is known to affect the metabolism of glucose; however, the underlying mechanism remains unclear. Therefore, we here investigated whether nicotine promoted the central regulation of glucose metabolism, which is closely linked to the circadian system. The oral intake of nicotine in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat content, and serum levels of insulin. Nicotine administered at the active period appears to be responsible for the effect on blood glucose, because nighttime but not daytime injections of nicotine lowered blood glucose levels in db/db mice. The chronic oral treatment with nicotine suppressed the mRNA levels of glucose-6-phosphatase, the rate-limiting enzyme of gluconeogenesis, in the liver of db/db and wild-type control mice. In the pyruvate tolerance test to evaluate hepatic gluconeogenic activity, the oral nicotine treatment moderately suppressed glucose elevations in normal mice and mice lacking dopamine receptors, whereas this effect was abolished in orexin-deficient mice and hepatic parasympathectomized mice. Under high-fat diet conditions, the oral intake of nicotine lowered blood glucose levels at the daytime resting period in wild-type, but not orexin-deficient, mice. These results indicated that the chronic daily administration of nicotine suppressed hepatic gluconeogenesis via the hypothalamic orexin-parasympathetic nervous system. Thus, the results of the present study may provide an insight into novel chronotherapy for type 2 diabetes that targets the central cholinergic and orexinergic systems.

scholarly journals 272.Decreased expression of oestrogen receptor β in the reproductive tract of pregnant relaxin-deficient (Rlx - / - ) mice

2004 ◽  
Vol 16 (9) ◽  
pp. 272
Author(s):  
J. T. McGuane ◽  
H. M. Gehring ◽  
L. J. Parry
Keyword(s):  
Transcriptional Activity ◽  
Reproductive Tract ◽  
Peptide Hormone ◽  
Mrna Levels ◽  
Wild Type ◽  
Taqman Probes ◽  
Pregnant Mice ◽  
Thermal Cycler ◽  
Deficient Mice ◽  
Ovariectomised Rats

The peptide hormone relaxin (RLX) is reported to directly affect uterine oestrogen receptors (ERs) in the rat (1). Treatment of immature ovariectomised rats with porcine RLX causes a decrease in uterine ERβ mRNA levels within 6 h. However, RLX has no effect on ERα expression. As both ERβ1 and ERβ2 inhibit ER-mediated transcriptional activity, this RLX-induced downregulation in ERβ could be a prerequisite for oestrogen to exert its effects on target tissues. The aim of the current study was to use relaxin-deficient (Rlx–/–) pregnant mice to investigate if relaxin deficiency results in alterations in either ERβ or ERα mRNA expression in reproductive tissues. Cervix and vagina tissues were obtained from adult C57/Blk6J wild-type mice at five stages of gestation (Days 7.5, 10.5, 14.5, 17.5, 18.5 pc) and Rlx–/– littermates on Days 7.5, 14.5 and 18.5 pc. Q-PCR with TaqMan probes in the Opticon 2 thermal cycler (MJ Research, GeneWorks) was used to quantify ERα and ERα gene expression. ERα mRNA levels were significantly (P < 0.05; ANOVA) increased in the cervix/vagina on Days 17.5 and 18.5 pc in Rlx+/+ mice. The increase in ERα in Rlx+/+ mice was negatively correlated with a significant decrease in ERβ expression from Day 14.5 pc. In contrast, there was no decrease in ERβ expression in the cervix/vagina of Rlx–/– mice; ERβ mRNA levels were significantly (P < 0.05) higher compared to Rlx+/+ mice on Days 14.5 or 18.5 pc. However, there was no corresponding reduction in ERα expression in the cervix/vagina of the Rlx–/– mice, so that ERα mRNA levels were still elevated at term despite the maintenance of high ERα expression. In summary, these data show changes in ERα expression in the cervix/vagina of relaxin-deficient mice, which may subsequently affect ERα-mediated transcriptional activity. (1) Pillai et al. (2002) Biol. Reprod. 67, 1919–1926.

scholarly journals Aquaporin 4 mRNA Levels in Neuromuscular Tissues of Wild-type and Dystrophin-deficient Mice

2008 ◽  
Vol 215 (4) ◽  
pp. 313-319 ◽  
Author(s):  
Seiji Shibuya ◽  
Hajime Hara ◽  
Yoshihiro Wakayama ◽  
Masahiko Inoue ◽  
Takahiro Jimi ◽  
...  
Keyword(s):  
Aquaporin 4 ◽  
Mrna Levels ◽  
Wild Type ◽  
Deficient Mice

scholarly journals Altered phenotype in LMAN1-deficient mice with low levels of residual LMAN1 expression

2020 ◽  
Vol 4 (22) ◽  
pp. 5635-5643
Author(s):  
Lesley A. Everett ◽  
Rami N. Khoriaty ◽  
Bin Zhang ◽  
David Ginsburg
Keyword(s):  
Human Subjects ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor V ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Wild Type ◽  
Cargo Proteins ◽  
Alpha 1 Antitrypsin ◽  
Deficient Mice

Abstract Combined deficiency of coagulation factors V and VIII (F5F8D) is an autosomal recessive bleeding disorder caused by loss-of-function mutations in either LMAN1 or MCFD2. The latter genes encode 2 components of a mammalian cargo receptor that facilitates secretion of coagulation factor V (FV) and factor VIII (FVIII) from the endoplasmic reticulum (ER) to the Golgi via coat protein complex II vesicles. F5F8D patients exhibit FV and FVIII levels that are ∼10% to 15% of normal. We report herein a comparative analysis for a series of murine Lman1 alleles. Consistent with previous reports, mice completely deficient in LMAN1 (Lman1−/−) exhibit ∼50% FV and FVIII levels. In contrast, mice carrying a hypomorphic Lman1 allele (Lman1cgt/cgt) that expresses ∼6% to 8% of wild-type Lman1 mRNA levels exhibit intermediate plasma FV and FVIII reductions (∼70% of wild-type levels). Lman1−/− mice exhibit ER accumulation of another LMAN1 cargo, alpha-1 antitrypsin (A1AT), with an intermediate level of A1AT ER retention observed in Lman1cgt/cgt mice. Finally, the previously reported strain-specific, partially penetrant, perinatal lethality of LMAN1-deficient mice (Lman1gt1/gt1) was confirmed in Lman1−/− mice, although it was not observed in Lman1cgt/cgt mice. Taken together, these results show a dose-dependent effect of residual LMAN1 on the secretion of its cargo proteins. The results also suggest that human subjects with hypomorphic LMAN1 mutations might present with mild bleeding phenotypes resulting from more modest reductions in FV and FVIII, which could be missed by routine clinical evaluation. Finally, these findings suggest that therapeutic targeting of LMAN1 to reduce FV and FVIII as an anticoagulant strategy may only require partial inhibition of LMAN1 function.

BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2515-2520 ◽  
Author(s):  
Léon Kautz ◽  
Delphine Meynard ◽  
Céline Besson-Fournier ◽  
Valérie Darnaud ◽  
Talal Al Saati ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hereditary Hemochromatosis ◽  
Bmp Signaling ◽  
Signaling Cascade ◽  
Mrna Levels ◽  
Wild Type ◽  
Smad Signaling ◽  
Hepcidin Expression ◽  
Hepcidin Mrna ◽  
Deficient Mice

Abstract Impaired regulation of hepcidin expression in response to iron loading appears to be the pathogenic mechanism for hereditary hemochromatosis. Iron normally induces expression of the BMP6 ligand, which, in turn, activates the BMP/Smad signaling cascade directing hepcidin expression. The molecular function of the HFE protein, involved in the most common form of hereditary hemochromatosis, is still unknown. We have used Hfe-deficient mice of different genetic backgrounds to test whether HFE has a role in the signaling cascade induced by BMP6. At 7 weeks of age, these mice have accumulated iron in their liver and have increased Bmp6 mRNA and protein. However, in contrast to mice with secondary iron overload, levels of phosphorylated Smads 1/5/8 and of Id1 mRNA, both indicators of BMP signaling, are not significantly higher in the liver of these mice than in wild-type livers. As a consequence, hepcidin mRNA levels in Hfe-deficient mice are similar or marginally reduced, compared with 7-week-old wild-type mice. The inappropriately low levels of Id1 and hepcidin mRNA observed at weaning further suggest that Hfe deficiency triggers iron overload by impairing hepatic Bmp/Smad signaling. HFE therefore appears to facilitate signal transduction induced by the BMP6 ligand.

scholarly journals Delayed Mortality and Attenuated Thrombocytopenia Associated with Severe Malaria in Urokinase- and Urokinase Receptor-Deficient Mice

2000 ◽  
Vol 68 (7) ◽  
pp. 3822-3829 ◽  
Author(s):  
Pierre Francois Piguet ◽  
Chen Da Laperrousaz ◽  
Christian Vesin ◽  
Fabienne Tacchini-Cottier ◽  
Giorgio Senaldi ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Plasminogen Activators ◽  
Tissue Type ◽  
Mrna Levels ◽  
Wild Type ◽  
Upa Receptor ◽  
Delayed Mortality ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT We explored the role of urokinase and tissue-type plasminogen activators (uPA and tPA), as well as the uPA receptor (uPAR; CD87) in mouse severe malaria (SM), using genetically deficient (−/−) mice. The mortality resulting from Plasmodium berghei ANKA infection was delayed in uPA−/− and uPAR−/−mice but was similar to that of the wild type (+/+) in tPA−/− mice. Parasitemia levels were similar in uPA−/−, uPAR−/−, and +/+ mice. Production of tumor necrosis factor, as judged from the plasma level and the mRNA levels in brain and lung, was markedly increased by infection in both +/+ and uPAR−/− mice. Breakdown of the blood-brain barrier, as evidenced by the leakage of Evans Blue, was similar in +/+ and uPAR−/− mice. SM was associated with a profound thrombocytopenia, which was attenuated in uPA−/− and uPAR−/− mice. Administration of aprotinin, a plasmin antagonist, also delayed mortality and attenuated thrombocytopenia. Platelet trapping in cerebral venules or alveolar capillaries was evident in +/+ mice but absent in uPAR−/− mice. In contrast, macrophage sequestration in cerebral venules or alveolar capillaries was evident in both +/+ and uPAR−/− mice. Polymorphonuclear leukocyte sequestration in alveolar capillaries was similar in +/+ and uPAR−/− mice. These results demonstrate that the uPAR deficiency attenuates the severity of SM, probably by its important role in platelet kinetics and trapping. These results therefore suggest that platelet sequestration contributes to the pathogenesis of SM.

TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure

2003 ◽  
Vol 285 (4) ◽  
pp. F610-F618 ◽  
Author(s):  
Ganesan Ramesh ◽  
W. Brian Reeves
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Mouse Kidney ◽  
Mrna Levels ◽  
Wild Type ◽  
Cisplatin Nephrotoxicity ◽  
Tnf Α ◽  
Apoptosis And Necrosis ◽  
Deficient Mice

Cisplatin produces acute renal failure in humans and mice. Previous studies have shown that cisplatin upregulates the expression of TNF-α in mouse kidney and that inhibition of either the release or action of TNF-α protects the kidney from cisplatin-induced nephrotoxicity. In this study, we examined the effect of cisplatin on the expression of TNF receptors TNFR1 and TNFR2 in the kidney and the role of each receptor in mediating cisplatin nephrotoxicity. Injection of cisplatin into C57BL/6 mice led to an upregulation of TNFR1 and TNFR2 mRNA levels in the kidney. The upregulation of TNFR2 but not TNFR1 was blunted in TNF-α-deficient mice, indicating ligand-dependent upregulation of TNFR2. To study the roles of each receptor, we administered cisplatin to TNFR1- or TNFR2-deficient mice. TNFR2-deficient mice developed less severe renal dysfunction and showed reduced necrosis and apoptosis and leukocyte infiltration into the kidney compared with either TNFR1-deficient or wild-type mice. Moreover, renal TNF-α expression, ICAM-1 expression, and serum TNF-α levels were lower in TNFR2-deficient mice compared with wild-type or TNFR1-deficient mice treated with cisplatin. These results indicate that TNFR2 participates in cisplatin-induced renal injury in mice and may play an important role in TNF-α-mediated inflammation in the kidney in response to cisplatin.

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