23 results on '"Mice as laboratory animals -- Research"'
Search Results
2. Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP)
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Mentor-Marcel, Roycelynn, Lamartiniere, Coral A., Eltoum, Isam A., Greenberg, Norman M., and Elgavish, Ada
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Prostate cancer -- Research ,Mice as laboratory animals -- Research ,Isoflavones -- Research ,Food/cooking/nutrition - Abstract
Studies in vitro suggest that osteopontin (OPN), an extracellular matrix protein secreted by macrophages infiltrating prostate tumors, and by tumor cells, may have a role in the transition from clinically insignificant tumors to metastatic prostate cancer (PC). Latent PC occurs at equal rates in Western and Asian men, but the incidence of advanced PC is many-fold higher in Western men. Our earlier studies in TRAnsgenic Mouse Prostate adenocarcinoma (TRAMP) mice showed that genistein, an isoflavone found in soybeans, lowered the incidence of advanced PC. This suggested that lower intake of dietary soy may be one possible cause for higher incidence of advanced PC in Western men. The objective of the present study was to test the hypothesis that genistein may exert its preventive effect by inhibiting OPN expression. From 5 to 28 wk of age, 80, 68, and 30 TRAMP mice were fed AIN-76A diet containing 0, 250, or 500 mg genistein/kg body weight, respectively. Organ weights were measured. The steady-state level of OPN mRNA was evaluated by RT-PCR in a longitudinal study in 74 TRAMP and 32 nontransgenic litter mates (NTM). Administration of 250 and 500 mg genistein/kg AIN-76A improved survival (P = 0.008 and P = 0.005, respectively) and reduced mean weight of prostates with poorly differentiated cancer (PD) (P < 0.001), as well as the mean weight of periaortic lymph nodes (LN), although the latter was not significant. OPN was upregulated 10-fold in PD compared with prostates with a lower pathological score from TRAMP or NTM of any age (P = 0.003). OPN mRNA levels in the dorsolateral prostate and metastasis to LN were significantly correlated (r = 0.643; P = 0.00006). Genistein had a dose-dependent, significant inhibitory effect on OPN transcript levels in prostates displaying advanced prostate cancer (PD; score 6; P = 0.05). Studies are consistent with the possibility that dietary genistein may delay the progression from benign to malignant tumors by inhibiting OPN expression. KEY WORDS: * genistein * prostate * osteopontin * TRAMP * cancer progression
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- 2005
3. Marginal maternal biotin deficiency in CD-1 mice reduces fetal mass of biotin-dependent carboxylases
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Sealey, Wendy M., Stratton, Shawna L., Mock, Donald M., and Hansen, Deborah K.
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Mice as laboratory animals -- Research ,Birth defects -- Research ,Biotin -- Research ,Vitamin deficiency -- Research ,Vitamin deficiency -- Risk factors ,Food/cooking/nutrition - Abstract
Marginal maternal biotin deficiency reduces hepatic activity of biotin-dependent carboxylases and causes high rates of fetal birth defects in mice. We tested the hypothesis that the decreased carboxylase activity observed in deficient dams and their offspring is mediated by decreased abundance of biotinylated carboxylases, decreased expression of their mRNAs, or both. During gestation, CD-1 mice were fed a diet that induced biotin deficiency or a biotin-sufficient diet. On gestational d 17, gravid uteri were removed, and each live fetus was examined grossly for defects. The expected high incidence of cleft palate (83%) in offspring was observed. In maternal and fetal liver, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and [beta]-methylcrotonyl-CoA carboxylase abundances were determined by Western blotting; the content of mRNAs for most of these enzymes and holocarboxylase synthetase was determined by real-time RT-PCR. Biotin deficiency significantly reduced the abundance of the carboxylases in maternal and fetal liver; neither the content of mRNAs for the carboxylases nor holocarboxylase synthetase changed. This study provides evidence that the decrease in carboxylase activities is attributable to a decrease in the abundance of biotinylated carboxylases; further, this effect is more severe in fetuses than dams. KEY WORDS: * biotin * biotin-dependent carboxylases * CD-1 mice * mRNA
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- 2005
4. Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats
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Reeves, Philip G., DeMars, Lana C.S., Johnson, W. Thomas, and Lukaski, Henry C.
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Copper in the body -- Health aspects ,Iron in the body -- Health aspects ,Mice as laboratory animals -- Research ,Food/cooking/nutrition - Abstract
The mechanism for reduced Fe absorption in Cu deficiency is unknown, but may involve the intestinal Cu-dependent ferroxidase, Hephaestin (Hp). A 2 x 2 factorial experiment was designed to include Cu-deficient (CUD) and Cu-adequate (CuA) male and female rats. Weanling rats of both sexes were randomly divided into 2 groups each and fed an AIN-93G diet with tow (< 0.3 mg/kg; CuD) or adequate Cu (5.0 mg/kg; CuA). After 19 d, rats were fed 1.0 g each of their respective diets labeled with [sup.59]Fe. Retained [sup.59]Fe was monitored by whole-body counting for 12 d. Then, rats were killed for [sup.59]Fe and Fe measurements in blood and various organs. Duodenal enterocytes were isolated for Western blot analysis of Hp. Signs of Cu and Fe deficiency were evident in both sexes. CuD male rats absorbed 60% as much Fe as CuA male rats (P < 0.001), whereas CuD female rats absorbed 70% (P < 0.001) as much as CuA females, with no difference between the sexes. Hp protein in enterocytes of CuD rats of both sexes was only 35% of that in CuA rats. The biological half-life of [sup.59]Fe in CuD rats was only 50% (P < 0.001) of that in CuA rats, suggesting that Fe turnover was faster in CuD rats than CuA rats. Serum, spleen, and kidney Fe were lower (P < 0.001) in CuD rats than in CuA rats. Duodenal mucosa and liver Fe were higher (P < 0.01) in CuD male rats than CuA rats. Duodenal Fe but not liver Fe was higher in CuD female rats than CuA rats. Liver Fe was much higher ( KEY WORDS: * copper deficiency * iron * absorption * biological half-life * rats
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- 2005
5. Metallothionein induction is not involved in cadmium accumulation in the duodenum of mice and rats fed diets containing high-cadmium rice or sunflower kernels and a marginal supply of zinc, iron, and calcium
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Reeves, Philip G., Chaney, Rufus L., Simmons, Robert W., and Cherian, M. George
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Diet therapy -- Research ,Metallothionein -- Health aspects ,Mice as laboratory animals -- Research ,Cadmium -- Health aspects ,Food/cooking/nutrition - Abstract
Rats fed diets with cadmium (Cd) concentrations similar to that found in human diets, and nutritionally marginal with respect to iron (Fe), zinc (Zn), and calcium (Ca) retained 10 times more Cd in the duodenum than rats fed adequate mineral diets. In the current study, 2 experiments were performed to determine the role of intestinal metallothionein (MT) in the accumulation of duodenal Cd, and to determine whether endogenous rice grain Cd is as available as Cd exogenously incorporated into the grain. In Expt. 1, wild-type and MT-null mice were fed 40% rice diets containing marginal or adequate amounts of Fe, Zn, and Ca, and 240 [micro]g Cd/kg. Duodenal Cd was 10 times higher in both wild-type and MT-null mice regardless of their mineral status. In Expt. 2, one group of rats was fed 40% rice diets in which Cd was incorporated into the rice during growth and maturation, and another group was fed 40% rice diets in which Cd was incorporated into the rice during cooking. Each group also was fed either marginal or adequate amounts of Zn, Fe, and Ca. After 5 wk, rats were given a single meal labeled with [sup.109]Cd, and the amount of label retained after 7 d was determined by whole-body counting. Rats with marginal mineral status retained 10 times more [sup.109]Cd than those with adequate status; however, there was no difference between rats fed endogenous or exogenous Cd rice. Although duodenal Cd concentration was 8 times higher in the marginally fed rats, MT concentration was unchanged. These 2 experiments indicate that MT induction is not involved in duodenal Cd accumulation in animals with marginal dietary status of Fe, Zn, and Ca. In addition, they support the hypothesis that marginal deficiencies of Fe, Zn, and Ca, commonly found in certain human populations subsisting on rice-based diets, play an important role in increasing the risk of dietary Cd exposure. KEY WORDS: * cadmium * metallothionein * MT-null mice * rats * rice
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- 2005
6. Dietary conjugated linoleic acid alleviates nonalcoholic fatty liver disease in Zucker (fa/fa) rats
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Nagao, Koji, Inoue, Nao, Wang, Yu-Ming, Shirouchi, Bungo, and Yanagita, Teruyoshi
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Mice as laboratory animals -- Research ,Liver diseases -- Diet therapy ,Linoleic acids -- Health aspects ,Food/cooking/nutrition - Abstract
Nonalcoholic fatty liver disease (NAFLD) is the preferred term to describe the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects both in vitro and in vivo. We tested whether dietary CLA protects Zucker (fa/fa) rats from hepatic injury. After 8 wk of feeding, hepatomegaly, hepatic triglyceride (TG) accumulation, and elevated hepatic injury markers in plasma were markedly alleviated in CLA-fed Zucker rats compared with linoleic acid-fed (control) rats. These effects were attributed in part to the enhanced hepatic activities of carnitine palmitoyltransferase, a key enzyme of fatty acid [beta]-oxidation, and microsomal TG transfer protein, an important factor for lipoprotein secretion due to the CLA diet. We previously reported that the severe hyperinsulinemia in control Zucker rats was attenuated in CLA-fed rats due to an enhanced level of plasma adiponectin, which improves insulin sensitivity. In the present study, the adiponectin concentration was increased and the mRNA expression of tumor necrosis factor-[alpha], an inflammatory cytokine, was markedly suppressed in the liver of CLA-fed Zucker rats. We speculate that the enhanced level of liver adiponectin may prevent the development and progression of NAFLD in CLA-fed Zucker rats. KEY WORDS: * conjugated linoleic acid * nonalcoholic fatty liver disease * adiponectin * tumor necrosis factor-[alpha] * Zucker (fa/fa) rats
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- 2005
7. Inhibition of hedgehog signaling protects adult mice from diet-induced weight gain
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Buhman, Kimberly K., Wang, Li Chun, Tang, Yuzhu, Swietlicki, Elzbieta A., Kennedy, Susan, Xie, Yan, Liu, Zhong-Yi, Burkly, Linda C., Levin, Marc S., Rubin, Deborah C., and Davidson, Nicholas O.
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Mice as laboratory animals -- Food and nutrition ,Mice as laboratory animals -- Health aspects ,Mice as laboratory animals -- Research ,Food/cooking/nutrition - Abstract
Hedgehog (Hh) signaling plays an important role in embryonic development of many tissues, including the gastrointestinal tract. Sonic Hh-and Indian Hh-deficient mice die before or soon after birth, precluding further study of this signaling pathway in the mature intestine. Maternal transfer of inactivating monoclonal antibodies to Hh proteins (anti-Hh moAb) during late stages of embryogenesis or to early postnatal mice produced intestinal villous abnormalities, progressive runting, and severe malabsorption of dietary fat. In the present study, we sought to determine the effect of inhibiting Hh signaling on weight gain and lipid absorption in adult mice. Anti-Hh moAb was administered to adult Balb/c mice fed either a low-fat, nonpurified diet or a high-fat, semipurified diet, and to adult ob/ob mice fed the low-fat, nonpurified diet. Weight gain was significantly inhibited by anti-Hh moAb treatment in Balb/C mice fed the high-fat, but not the low-fat diet and in ob/ob mice. Further analysis of adult Balb/c mice fed the high-fat diet demonstrated that although total lipid absorption was normal, the rate of triglyceride absorption was significantly delayed in mice treated with anti-Hh moAb and they had significantly increased fecal FFA excretion. Hepatic steatosis, found in high-fat fed Balb/c mice treated with the control moAb, was abrogated by anti-Hh moAb administration. These findings point to a potential role for Hh signaling pathways in diet-induced abnormalities of lipid metabolism. J. Nutr. 134: 2979-2984, 2004. KEY WORDS: * hedgehog signaling * intestinal triglyceride absorption * hepatic steatosis
- Published
- 2004
8. Mice deficient in methylenetetrahydrofolate reductase exhibit tissue-specific distribution of folates
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Ghandour, Haifa, Chen, Zhoutao, Selhub, Jacob, and Rozen, Rima
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Mice as laboratory animals -- Food and nutrition ,Mice as laboratory animals -- Research ,Food/cooking/nutrition - Abstract
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), which is used for homocysteine remethylation to methionine, the precursor of S-adenosylmethionine (SAM). Impairment of MTHFR will increase homocysteine levels and compromise SAM-dependent methylation reactions. Mild MTHFR deficiency is common in many populations due to a polymorphism at bp 677. To assess how impaired MTHFR activity affects folate metabolism in various tissues in vivo, we used affinity/HPLC with electrochemical detection to analyze the distribution of folates in plasma, liver, and brain of Mthfr-deficient mice. The most pronounced difference in total folate was observed in plasma. In Mthfr -/- mice, plasma total folate levels, were ~25% of those in wild-type (Mthfr +/+) mice. Only 40% of plasma folate in Mthfr -/- mice was comprised of 5-methylTHF, compared with at least 80% in the other 2 genotype groups. In liver and brain, there were no differences in total folate. However, the proportion of 5-methylTHF in both tissues was again markedly reduced in mice with the Mthfr -/- genotype. In this genotype group, 5-methylTHF is likely derived from the diet. Our study demonstrated reduced total circulatory folate and altered distribution of folate derivatives in liver and brain in Mthfr deficiency. Decreased methylfolates and increased nonmethylfolates would affect the flux of one-carbon units between methylation reactions and nucleotide synthesis. This altered flux has implications for several common disorders, including cancer and vascular disease. J. Nutr. 134: 2975-2978, 2004. KEY WORDS: * folate distribution * methyltetrahydrofolate * formylated-folates * MTHFR deficiency
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- 2004
9. Antitumor effects of various low-molecular-weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180-bearing mice
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Maeda, Yasunori and Kimura, Yoshiyuki
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Mice as laboratory animals -- Research ,Lymphocytes ,Chitin ,Food/cooking/nutrition - Abstract
Various low-molecular-weight chitosans such as the 21-kDa, 46-kDa, and 120-kDa chitosans obtained by enzymatic hydrolysis of a high-molecular-weight chitosan (average molecular weight, 650 kDa) had low viscosity and were water soluble. We examined the antitumor activity of various water-soluble chitosans with different molecular weights in sarcoma 180-bearing mice. A 21 -kDa water-soluble chitosan and oligochitosan (100 and 300 mg/kg body) administered by i.g. intubation reduced the tumor growth and final tumor weight in sarcoma 180-bearing mice. A 46-kDa water-soluble chitosan at a dose of 100 mg/kg body reduced the tumor growth and final tumor weight, but had no effect at 300 mg/kg. On the other hand, a 130-kDa water-soluble chitosan had no effect on tumor growth. The 21- and 46-kDa chitosans (10 mg/L) enhanced the natural killer (NK) activity in intestinal intraepithelial lymphocytes (IELs) or splenic lymphocytes. The NK activity of low-molecular-weight chitosan (21- and 46-kDa chitosans)-treated IELs or splenic lymphocytes was stronger than that of high-molecular-weight chitosan (130- and 650-kDa chitosans)-treated IELs or splenic lymphocytes. In addition, low-molecular-weight chitosan-treated IELs or splenic lymphocytes also enhanced the cytotoxic activity against sarcoma 180 cells. In an in vivo study, although low-molecular-weight chitosan-treated IELs had cytotoxic activity against tumor cells, splenic lymphocytes treated with chitosans had no effect. These findings suggest that the antitumor activity of low-molecular-weight chitosans (12- and 46-kDa chitosans) and oligochitosan might be due in part to the enhancement of NK activity in IELs. Thus, the low-molecular-weight chitosans or oligochitosan might be useful in preventing tumor growth through the activation of intestinal immune functions. J. Nutr. 134: 945-950, 2004. KEY WORDS: * water-soluble chitosan * low-molecular-weight chitosan * antitumor activity * intestinal intraepithelial lymphocytes * natural killer activity
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- 2004
10. Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-isomer of linoleic acid
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Degrace, P., Demizieux, L., Gresti, J., Chardigny, J.-M., Sebedio, J.-L., and Clouet, P.
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Mice as laboratory animals -- Research ,Liver diseases ,Adipose tissues ,Linoleic acids ,Food/cooking/nutrition - Abstract
Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those of CLA1 in mice fed CLA1. The mitochondrial protein content per total liver was about 56% greater in CLA2-fed mice than in CLA1-fed mice and controls. Mitochondrial carnitine palmitoyltransferase I (CPT I) and carnitine-dependent palmitate oxidation activities were also significantly greater in CLA2-fed mice than in the two other groups. The amounts of malonyl-CoA per gram of liver and the sensitivity of CPT I to malonyl-CoA inhibition were greater in both groups of CLA-fed mice than in the controls. L-CPT I mRNA expression doubled in CLA2-fed mice and was 3 and 2 times greater for M-CPT I in the CLA1 and CLA2 groups, respectively, compared with controls. Peroxisomal FA oxidation-related activities and acyl-CoA oxidase mRNA expression were increased in CLA1-fed mice, and to a larger extent in CLA2-fed mice, relative to controls. These data indicate that FA oxidation capacities were increased in mice fed CLA2, but were likely depressed in vivo through malonyl-CoA inhibition. KEY WORDS: * acetyl-CoA carboxylase * acyl-CoA oxidase * carnitine palmitoyltransferase I * malonyl-CoA * regulation
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- 2004
11. Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice
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Elsherif, Laila, Wang, Lipeng, Saari, Jack T., and Kang, Y. James
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Heart diseases -- Risk factors ,Cardiomyopathy -- Risk factors ,Mice as laboratory animals -- Research ,Copper in the body ,Food/cooking/nutrition - Abstract
Dietary copper deficiency (CUD) leads to cardiac hypertrophy in various animal models. We showed recently that heart failure develops after hypertrophy in FVB mice fed a CuD diet. The present study was undertaken to determine whether CuD-induced cardiac failure is reversible upon copper repletion (CUR). Dams of FVB mice were fed a CuD diet (0.3 mg/kg) starting from d 3 postdelivery; the weanling pups were fed the same diet until CuR with 6.0 mg/kg Cu in the diet at 4 or 5 wk of age. CuR at 4 wk of age prevented the body weight loss; at 5 wk of age, it resulted in the regaining of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the CuR mice. Histopathological examination revealed that CuR eliminated CuD-caused lipid deposition in the myocardium, and electron microscopy demonstrated that CuD-induced ultrastructural changes such as mitochondrial swelling and organelle structural disarray were all reversed in the CuR mice. Hemodynamic analysis showed that the CuD-depressed systolic and diastolic parameters such as the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt), and the contraction and relaxation times were completely recovered in the CuR mice. Furthermore, the CuD-blunted myocardial responses to the [beta]-adrenergic agonist, isoproterenol, were also restored in the CuR mice. This study thus demonstrates for the first time that CuR results in the regression of heart failure induced by CuD as demonstrated by the reversal of depressed cardiac hemodynamic and contractile function and the restored responsiveness to [beta]-adrenergic stimulation. KEY WORDS: * cardiomyopathy * cardiac function * copper deficiency * copper repletion * heart hypertrophy
- Published
- 2004
12. Mice heterozygous for Atp10c, a putative amphipath, represent a novel model of obesity and type 2 diabetes
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Dhar, Madhu S., Sommardahl, Carla S., Kirkland, Tanisa, Nelson, Sarah, Donnell, Robert, Johnson, Dabney K., and Castellani, Lawrence W.
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Mice as laboratory animals -- Research ,Type 2 diabetes ,Obesity ,Insulin resistance ,Heterozygosis ,Food/cooking/nutrition - Abstract
Atp10c is a novel type IV P-type ATPase and is a putative phospholipid transporter. The purpose of this study was to assess the overall effect of the heterozygous deletion of Atp10c on obesity-related phenotypes and metabolic abnormalities in mice fed a high-fat diet. Heterozygous mice with maternal inheritance of Atp10c were compared with heterozygous mice with paternal inheritance of Atp10c and wild-type controls. Body weight, adiposity index, and plasma insulin, leptin and triglyceride concentrations were significantly greater in the mutants inheriting the deletion maternally compared with their sex- and age-matched control male mice fed a 10% fat (% energy) diet and female mice fed a 45% fat (% energy) diet. Glucose and insulin tolerance tests were performed after mice consumed the diets for 4 and 8 wk. Mutants had altered glucose tolerance and insulin response compared with controls, suggesting insulin resistance in both sexes. Mice were killed at 12 wk and routine gross and histological evaluations of the liver, pancreas, adipose tissue, and heart were performed. Histological evaluation showed micro- and macrovesicular lipid deposition within the hepatocytes that was more severe in the mutant mice than in age-matched controls. Although sex differences were observed, our data suggest that heterozygous deletion along with an unusual pattern of maternal inheritance of the chromosomal region containing the single gene, Atp10c, causes obesity, type 2 diabetes, and nonalcoholic fatty liver disease in these mice. KEY WORDS: * mouse chromosome 7 * Atp10c, type IV P-type ATPase * insulin resistance
- Published
- 2004
13. Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice
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Lim, Yunsook, Levy, Mark, and Bray, Tammy M.
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Mice as laboratory animals -- Research ,Zinc deficiency diseases ,Wound healing ,Inflammation ,Food/cooking/nutrition - Abstract
Zinc deficiency is a well-known health problem associated with delayed wound healing, yet the precise mechanisms that underlie the delay remain unknown. We hypothesized that zinc deficiency delays wound healing as a result of decreased nuclear factor (NF)[kappa]B activation, reduced expression of proinflammatory cytokines [interleukin (IL)-1[beta] and tumor necrosis factor (TNF)-[alpha]], and a decrease in neutrophil infiltration during the early stage of cutaneous wound healing. We used a cutaneous, full-thickness excisional wound model in CD-1 mice to examine the rate of wound closure as well as mRNA levels of inhibitory (I)[kappa]B[alpha], IL-1[beta], and TNF-[alpha] and infiltration of neutrophils at the wound site of mice fed a diet containing KEY WORDS: * wound healing * zinc * inflammation * proinflammatory cytokines
- Published
- 2004
14. New leptin receptor mutations in mice: [Lepr.sup.db-rtnd], [Lepr.sup.db-dmpg] and [Lepr.sup.db-rlpy]
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Kim, Jung Han, Taylor, Paul N., Young, Dawn, Karst, Son Yong, Nishina, Patsy M., and Naggert, Jurgen K.
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Gene mutations -- Analysis ,Mice as laboratory animals -- Research ,Mice as laboratory animals -- Genetic aspects ,Leptin -- Genetic aspects ,Nutrition -- Research ,Food/cooking/nutrition - Abstract
Three new spontaneous recessive mouse mutations in the leptin receptor gene (Lepr), [Lepr.sup.db-rtnd], [Lepr.sup.db-dmpg] and [Lepr.sup.db-rlpy], originated in the CBA/J (CBA), B10.D2-[H8.sup.b](57N)/Sn (B10) and NU/J strains, respectively. [Lepr.sup.db-rtnd] and [Lepr.sup.db-dmpg] were maintained on C57BL/6J (B6), resulting in congenic lines of B6.CBA-[Lepr.sup.db-rtnd] and B6.B10-[Lepr.sup.db-dmpg]. [Lepr.sup.db-rtnd] was also maintained on CBA post F1 generation of a cross between the B6 and the CBA, generating the congenic line CBA.B6CBA-[Lepr.sup.db-rtnd]. [Lepr.sup.db-rlpy] was maintained as a coisogenic strain. The aims of this study were to determine the molecular bases for these new Lepr mutations and to characterize the new mutant stocks, with respect to obesity and diabetes. Mutations were analyzed by Southern blot analysis, reverse transcriptase-polymerase chain reaction and sequencing. Body weights and plasma glucose and insulin levels were measured, and the histology of the pancreas was carried out. [Lepr.sup.db-rtnd] contained one G deletion in exon 4 of Lepr, introducing a frameshift and premature termination. [Lepr.sup.db-dmpg] had a deletion in the extracellular domain of Lepr. [Lepr.sup.db-rlpy] exhibited a large DNA deletion, leading to a complete lack of Lepr. All three mutations led to morbid obesity and diabetes. It is noteworthy that [Lepr.sup.db-rtnd] caused milder hyperglycemia accompanied by higher plasma and pancreatic insulin contents on B6 compared to that on CBA backgrounds. In summary, we discovered three new mutations of Lepr, providing new mouse models for obesity and diabetes. Furthermore, our mutant stocks will be useful in elucidating the effects of the genetic background on the Lepr mutations and in testing the specificity of antibodies to LEPR. KEY WORDS: * coisogenic * congenic * Lepr * mice * mutations
- Published
- 2003
15. Reduced glucose consumption in the Curly Tail mouse does not initiate the pathogenesis leading to spinal neural tube defects
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Peeters, Marian C.E., Geelen, Jan L.M.C., Hekking, Johan W.M., Chavannes, Niels, Geraedts, Joep P.M., and Straaten, Henny W.M. van
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Mice as laboratory animals -- Research ,Neural tube -- Abnormalities ,Glucose -- Research ,Food/cooking/nutrition - Abstract
At embryonic stages of neural tube closure, the mouse embryo exhibits a high rate of glycolysis with glucose as the main energy source. In the curly tail mouse, often used as model system for study of human neural tube defects, a delay in closure of the posterior neuropore (PNP) is proposed to be indirectly caused by a proliferation defect in the caudal region. Because glucose is important for proliferation, we tested glucose uptake in curly tail and control embryos, and in a BALB/c-curly tail recombinant strain. The structure and expression of Glut-1, a glucose transporter molecule that is abundantly present during those embryonic stages and that has been mapped in the region of the major curly tail gene, were also studied; however, no strain differences could be demonstrated. Glucose uptake was determined by measuring glucose depletion from the medium in long-term embryo cultures that encompassed the stages of PNP closure and by measuring accumulation of 3H-deoxyglucose in short-term cultures at the stages of early and final PNP closure. Both approaches indicated a reduced glucose uptake by curly tail and recombinant embryos. Surprisingly, the uptake per cell appeared normal, accompanied by a significantly lower DNA content of the mutant embryos. Therefore, it is unlikely that reduced cell proliferation is caused by a reduction in glucose supply during the pathogenesis of the defects in curly tail embryos. The reduced DNA content as well as the reduced glucose uptake per embryo are likely downstream effects of the aberrant proliferation pattern. KEY WORDS: * mouse embryo * curly tail * neural tube defects * glucose * Glut-1
- Published
- 1998
16. Dietary lutein from marigold extract inhibits mammary tumor developments in BALB/c mice
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Park, Jean Soon, Chew, Boon P., and Wong, Teri S.
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Carotenoids -- Physiological aspects ,Breast cancer -- Research ,Tumors -- Research ,Antioxidants -- Research ,Mice as laboratory animals -- Research ,Food/cooking/nutrition - Abstract
High levels of dietary lutein can inhibit mammary tumor growth in mice. However, the antitumor effect of low levels of dietary lutein on mammary tumors is unavailable. Female BALB/c mice and the WAZ-2T (-SA) mammary tumor cell line were used in two experiments. A preliminary tumor cell dose titration study (Experiment 1) was designed to determine the inoculation dose to produce [approximately]65% tumor incidence. Mice (n = 10/dose) were inoculated with 0 to 1 x [10.sup.6] tumor cells in the right inguinal mammary fat pad. A tumor cell load of 2.5 x [10.sup.3] cells/inoculation produced [approximately]65% tumor incidence. This dose was used in a subsequent study (Experiment 2) of the efficacy of dietary lutein against mammary tumor development. Mice (n = 20/treatment) were fed a semisynthetic diet containing 0, 0.002, 0.02, 0.2 or 0.4% lutein from marigold extract. After 14 d, all mice were inoculated with 2.5 x [10.sup.3] tumor cells, and tumor growth was measured daily for 70 d at which time blood, liver, spleen and tumors were obtained. Lutein + zeaxanthin uptake increased dose-dependently (P < 0.05) with dietary lutein levels from 0 to 0.02% (spleen) or 0.2% (plasma, liver and tumor). Low levels (0.002 and 0.02%) of dietary lutein lowered (P < 0.05) mammary tumor incidence, tumor growth and lipid peroxidation, and increased tumor latency, whereas higher dietary levels (0.2 or 0.4%) were less effective. Therefore, very low amounts of dietary lutein (0.002%) can efficiently decrease mammary tumor development and growth in mice. Key Words: * lutein * mammary tumor * antioxidant * mice
- Published
- 1998
17. In vivo glucose contribution to glutamate synthesis is maintained while its contribution to acetyl CoA is lowered in adult mice fed a diet with a high fat: carbohydrate ratio
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Pascual, Monica, Jahoor, Farouk, and Reeds, Peter J.
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Mice as laboratory animals -- Research ,Carbohydrates in the body -- Health aspects ,High-carbohydrate diet -- Health aspects ,Low-carbohydrate diet -- Health aspects ,Glucose metabolism -- Health aspects ,Food/cooking/nutrition - Abstract
To investigate the contribution of dietary carbohydrate to glutamate and acetyl CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low-carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee ratios of [13[C.sub.3]] and [13[C.sub.6]]blood glucose and of the [13[C.sub.2]] and [13[C.sub.3]] isotopomers of blood, mucosal, hepatic and muscle alanine and glutamate were used to calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33 and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P < 0.01) in the liver and muscle of the LCD group, respectively, but was unaltered in the mucosa. Glucose made a minor contribution to glutamate synthesis via oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction of hepatic and muscle glutamate synthesis derived from glucose was not affected by the diet. We conclude that glucose oxidation in liver and muscle parallels the contribution of carbohydrate to dietary energy and that glucose is not a major carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in extraintestinal tissues is preserved when dietary carbohydrate is restricted. KEY WORDS: dietary glucose metabolism; stable isotopes; glutamate synthesis; acetyl CoA synthesis; mice
- Published
- 1998
18. Chronic but Not Acute Energy Restriction Increases Intestinal Nutrient Transport in Mice
- Author
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Ferraris, Ronaldo P., Cao, Qing-Xue, and Prabhakaram, Shyam
- Subjects
Intestines -- Research ,Nutrient interactions -- Research ,Mice as laboratory animals -- Research ,Aging -- Health aspects ,Metabolism -- Research ,Food/cooking/nutrition - Abstract
Chronic energy restriction (ER) dramatically enhances intestinal absorption of nutrients by aged mice. Do adaptations in nutrient absorption develop only after extended ER or immediately after its initiation? To determine the time course of adaptations, we measured rates of intestinal glucose, fructose and proline transport 1-270 d after initiation of ER (70% of ad libitum) in 3-mo old mice. Mice of the same age that consumed food ad libitum (AL) served as controls; a third group was starved for 1 or 2 d only, to distinguish the effects of acute ER from those of starvation. Acute ER of 1, 2 and 10 d had no effect on nutrient absorption. Starvation significantly decreased intestinal mass per centimeter, thereby reducing transport per centimeter and intestinal absorptive capacity without significantly altering transport per milligram of intestine. ER for 24 d enhanced only fructose uptake, whereas ER for 270 d enhanced uptake of all nutrients by 20-100%. Despite marked differences in body weights, the wet weights of the stomach, small intestine, cecum and large intestine were generally similar in AL and ER mice, suggesting that the gastrointestinal tract was spared during ER. In contrast, the wet weights of the lungs, kidneys, spleen, heart, pancreas and liver each differed by 40-120% between ER and AL mice. Intestinal transport adaptations develop gradually during ER, and the main mechanism underlying these adaptations is a dramatic increase in transport activity per milligram tissue. J. Nutr. 131: 779-786, 2001. KEY WORDS: * aging and diet * internal organs * intestines and metabolism * mice * nutrient transport
- Published
- 2001
19. The neurobiology of selenium: lessons from transgenic mice
- Author
-
Schweizer, Ulrich, Schomburg, Lutz, and Savaskan, Nicolai E.
- Subjects
Mice as laboratory animals -- Research ,Selenium ,Proteins ,Neurobiology ,Glutathione ,Food/cooking/nutrition - Abstract
The brain represents a privileged organ with respect to selenium (Se) supply and retention. It contains high amounts of this essential trace element, which is efficiently retained even in conditions of Se deficiency. Accordingly, no severe neurological phenotype has been reported for animals exposed to Se-depleted diets. They are, however, more susceptible to neuropathological challenges. Recently, gene disruption experiments supported a pivotal role for different selenoproteins in brain function. Using these and other transgenic models, longstanding questions concerning the preferential supply of Se to the brain and the hierarchy among the different selenoproteins are readdressed. Given that genes for at least 25 selenoproteins have been identified in the human genome, and most of these are expressed in the brain, their specific roles for normal brain function and neurological diseases remain to be elucidated. KEY WORDS: * selenoprotein P * glutathione peroxidase * tRNASec * MsrB * thioredoxin reductase
- Published
- 2004
20. Does tissue glutathione level indicate organ senescence?
- Subjects
Cysteine -- Physiological aspects ,Mice as laboratory animals -- Research ,Glutathione -- Physiological aspects ,Aging -- Genetic aspects ,Cells -- Aging ,Food/cooking/nutrition - Published
- 1989
21. Dietary choline and synaptic morphology in mice
- Subjects
Mice as laboratory animals -- Research ,Choline -- Physiological aspects ,Synapses -- Research ,Food/cooking/nutrition - Published
- 1987
22. The initiation and growth of tumors; Introduction. I: Effects of underfeeding
- Author
-
Tannenbaum, Albert
- Subjects
Nutritionally induced diseases -- Research ,Tumors -- Causes of ,Mice as laboratory animals -- Research ,Skin cancer -- Research ,Breast cancer ,Food/cooking/nutrition - Published
- 1987
23. Treatment for vCJD seems theoretical possible
- Subjects
Creutzfeldt-Jakob disease -- Research ,Monoclonal antibodies -- Research ,Mice as laboratory animals -- Research ,Scrapie -- Research ,Consumer news and advice ,Food/cooking/nutrition ,Government - Abstract
Researchers in the UK have shown that a future treatment for the new variant form of Creutzfeld-Jacob disease and similar diseases could be possible. The British scientists used monoclonal antibodies [...]
- Published
- 2003
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