Thrombospondin-1 Gene Expression Affects Survival and Tumor Spectrum of p53-Deficient Mice

Objective— Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E–deficient mice and the underlying mechanism. Approach and Results— Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E–deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Conclusions— Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.

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Consumption of Soy Protein Isolate Reduces Hepatic SREBP-1c and Lipogenic Gene Expression in Wild-Type Mice, but Not in FXR-Deficient Mice

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.110224 ◽

2011 ◽

Vol 75 (9) ◽

pp. 1702-1707 ◽

Cited By ~ 12

Author(s):

Tsutomu HASHIDUME ◽

Takashi SASAKI ◽

Jun INOUE ◽

Ryuichiro SATO

Keyword(s):

Gene Expression ◽

Soy Protein ◽

Soy Protein Isolate ◽

Protein Isolate ◽

Wild Type ◽

Lipogenic Gene ◽

Lipogenic Gene Expression ◽

Deficient Mice

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Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C

Genetics and Molecular Biology ◽

10.1590/s1415-47572011005000031 ◽

2011 ◽

Vol 34 (3) ◽

pp. 386-395 ◽

Cited By ~ 9

Author(s):

Yan Jiao ◽

Jifei Zhang ◽

Jian Yan ◽

John Stuart ◽

Griffin Gibson ◽

...

Keyword(s):

Gene Expression ◽

Vitamin C ◽

Differential Gene Expression ◽

Wild Type ◽

Differential Gene ◽

Deficient Mice

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Neurotensin Gene Expression and Behavioral Responses Following Administration of Psychostimulants and Antipsychotic Drugs in Dopamine D3 Receptor Deficient Mice

Neuropsychopharmacology ◽

10.1016/s0893-133x(00)00179-2 ◽

2001 ◽

Vol 24 (2) ◽

pp. 170-182 ◽

Cited By ~ 31

Author(s):

C Betancur

Keyword(s):

Gene Expression ◽

Antipsychotic Drugs ◽

Behavioral Responses ◽

Dopamine D3 Receptor ◽

D3 Receptor ◽

Dopamine D3 ◽

Deficient Mice

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Abstract 63: ACE2 Deficiency Reduces Insulin Content of Isolated Pancreatic Islets and Plasma Insulin Concentrations Post-Glucose Challenge in Obese C57BL/6 Mice

Hypertension ◽

10.1161/hyp.62.suppl_1.a63 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Robin C Shoemaker ◽

Lisa A Cassis

Keyword(s):

Gene Expression ◽

Insulin Secretion ◽

Pancreatic Islets ◽

Plasma Insulin ◽

Insulin Content ◽

Isolated Pancreatic Islets ◽

Diet Induced Obesity ◽

Glucose Challenge ◽

Ace2 Gene ◽

Deficient Mice

Objective: Diet-induced obesity promotes type 2 diabetes (T2D). Drugs that inhibit the renin-angiotensin system (RAS) have been demonstrated in clinical trials to decrease the onset of T2D. Angiotensin converting enzyme 2 (ACE2) negatively regulates the RAS by catabolizing angiotensin II (AngII). Preliminary data indicate that ACE2 deficient mice display impairments in glucose homeostasis at 8 weeks of age. We tested the hypothesis that ACE2 deficiency promotes the development of glucose intolerance and β-cell dysfunction in mice with diet-induced obesity. Methods and Results: Male Ace2 +/y or -/y mice were fed a low fat (LF, 10% kcal as fat) or high fat (HF, 60% kcal as fat) diet for 5 or 17 weeks. After 5 weeks, plasma insulin concentrations (0, 30 min) following a glucose challenge were significantly greater in HF versus ( vs) LF-fed mice. However, glucose-stimulated increases in plasma insulin concentrations were decreased in HF-fed ACE2 deficient mice compared to controls (2.96 ± 0.18 vs 4.44 ± 0.40 ng/ul, respectively; P<0.01). Surprisingly, isolated pancreatic islets from HF-fed mice of either genotype released similar concentrations of insulin in response to glucose. However, mRNA abundance of insulin was significantly reduced in islets from HF-fed Ace2 -/y compared to +/y mice (1.76 ± 0.17 vs 2.54 ± 0.18 insulin/18S ratio; P<0.05). After 17 weeks, the plasma insulin response to glucose was further reduced in the HF-fed ACE2 deficient mice compared to controls (8.07 ± 0.98 vs 13.90 ± 1.10 ng/ul; P<0.01). Further, LF-fed ACE2 deficient mice also displayed reductions in plasma glucose-stimulated insulin concentrations (1.92 ± 0.98 vs 3.09 ± 0.98 ng/ul; P<0.01). Islets from HF-fed wild type mice displayed reduced ACE2 gene expression compared to LF (0.069 ± 0.009 vs 0.169 ± 0.01, ACE2/18S ratio; P<0.001) and AngII totally suppressed islet glucose-stimulated insulin secretion compared to vehicle (-0.16 ± 0.18 vs 0.9 ± 0.26, fold change over basal; P<0.05). Conclusions: These results demonstrate that ACE2 deficiency promotes the development of T2D by regulating islet insulin content. Moreover, diet-induced obesity reduces islet ACE2 gene expression with augmented AngII-induced impairment of insulin secretion.

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The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice

Development ◽

10.1242/dev.125.12.2315 ◽

1998 ◽

Vol 125 (12) ◽

pp. 2315-2325 ◽

Cited By ~ 19

Author(s):

E.A. Grove ◽

S. Tole ◽

J. Limon ◽

L. Yip ◽

C.W. Ragsdale

Keyword(s):

Gene Expression ◽

Cerebral Cortex ◽

Choroid Plexus ◽

Gene Families ◽

Cubitus Interruptus ◽

Embryonic Mouse ◽

Developmental Relationship ◽

Cortical Hem ◽

Deficient Mice

In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.

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