Data on dysfunctional muscle contraction and genes contractile expression associated with chlorpyrifos exposure in slow twitch skeletal muscle.

Chlorpyrifos (CPF) is a toxic organophosphate commonly used worldwide. Its residues are being detected in different environmental matrixes and hence in the food chain. Repeated CPF exposure might pose health risk for the general population on long term. This data article contains the data of contractility impairment further to dietary exposure to CPF on a hind limb skeletal muscle; soleus, a typical slow twitch skeletal muscle. Thirty adult male rats Sprague Dawley are divided into three groups receiving the following daily diet for 6 weeks: Group 1 (vehicle), Group 2: CPF1 (CPF 1mg/kg/day) and Group 3: CPF5 (CPF 5 mg/kg/day). Soleus twitch tension and fatigability index are determined at the end of the treatment. The activity of acteylcholinesterase enzyme is assessed in the tissues homogenate. Additionally, we examined the expression levels of ryanodine type 1 receptor (RyR1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 1 (Atp2a1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2 (Atp2a2) and nicotinic acetylcholine receptor (nAChR) in CPF-exposed skeletal muscle tissue using quantitative real time polymerase chain reaction. CPF exposure at two different doses induced an increase in twitch contraction in soleus muscle along with an increase in fatigability index. These increases are accompanied by low level of acetylcholinesterase enzyme activity as well as modification in genes level expression of nAChR, RyR1, Atp2a1 and Atp2a2 involved in contractility.

Global gene expression analysis of Escherichia coli K-12 DH5α after exposure to 2.4 GHz wireless fidelity radiation.

This study investigated the non-thermal effects of Wi-Fi radiofrequency radiation of 2.4 GHz on global gene expression in Escherichia coli K-12 DH5α. High-throughput RNA-sequencing of 2.4 GHz exposed and non-exposed bacteria revealed that 101 genes were differentially expressed (DEGs) at P ≤ 0.05. The up-regulated genes were 52 while the down-regulated ones were 49. QRT-PCR analysis of pgaD, fliC, cheY, malP, malZ, motB, alsC, alsK, appB and appX confirmed the RNA-seq results. About 7% of DEGs are involved in cellular component organization, 6% in response to stress stimulus, 6% in biological regulation, 6% in localization, 5% in locomotion and 3% in cell adhesion. Database for annotation, visualization and integrated discovery (DAVID) functional clustering revealed that DEGs with high enrichment score included genes for localization of cell, locomotion, chemotaxis, response to external stimulus and cell adhesion. Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that the pathways for flagellar assembly, chemotaxis and two-component system were affected. Go enrichment analysis indicated that the up-regulated DEGs are involved in metabolic pathways, transposition, response to stimuli, motility, chemotaxis and cell adhesion. The down-regulated DEGs are associated with metabolic pathways and localization of ions and organic molecules. Therefore, the exposure of E. coli DH5α to Wi-Fi radiofrequency radiation for 5 hours influenced several bacterial cellular and metabolic processes.

The impact of exposure of diabetic rats to 900 MHz electromagnetic radiation emitted from mobile phone antenna on hepatic oxidative stress.

The excessive exposure of patients with type 2 diabetes mellitus (T2DM) to electromagnetic radiation (EMR) from mobile phones or their base stations antenna may influence oxidative stress and development of diabetic complications. Here, we investigated the effects of exposing type 2 diabetic rats to EMR of 900 MHz emitted from GSM mobile phone antenna for 24 hours/day over a period of 28 days on hyperglycemia and hepatic oxidative stress. Male Sprague-Dawley rats were divided into 4 groups (12 rats/group): control rats, normal rats exposed to EMR, T2DM rats generated by nicotinamide/streptozotocin administration, and T2DM rats exposed to EMR. Our results showed that the exposure of T2DM rats to EMR nonsignificantly reduced the hyperglycemia and hyperinsulinemia compared to unexposed T2DM rats. The exposure of T2DM rats to EMR for 28 days increased the hepatic levels of MDA and Nrf-2 as well as the activities of superoxide dismutase (SOD) and catalase but decreased phosphorylated Akt-2 (pAkt-2) as compared to unexposed T2DM rats. Therefore, the decrease in the hepatic pAkt-2 in T2DM rats after the exposure to EMR may result in elevated level of hepatic MDA, even though the level of Nrf-2 and the activities of SOD and catalase were increased. Abbreviations: BGL: blood glucose level; EMR: electromagnetic radiation; GSM: global system for mobile communication; H2O2: hydrogen peroxide; LSD: least significance difference; MDA:malondialdehyde; Nrf-2: nuclear factor erythroid 2- related factor 2; PI3K: phosphoinositide-3-kinase; pAkt-2: phosphorylated Akt-2; Akt-2: protein kinase; ROS: reactive oxygen species; SEM: standard error of the mean; STZ: streptozotocin; SOD: superoxide dismutase ; O2-: superoxide radical; CT: threshold cycle; T2DM: type 2 diabetes mellitus.

Impacts of prolonged chlorpyrifos exposure on locomotion and slow-and fast- twitch skeletal muscles contractility in rats.

AIM: Investigate the effect of dietary exposure to chlorpyrifos on locomotion and contraction of soleus andextensor digitorum longus (edl) involved in locomotion. Methods: Rats were fed diets containing 1 or 5 mg kg-1 of chlorpyrifos for six weeks. Locomotion has been assessed weekly using beam walking and beam balance tests. Soleus and edl were removed to study contractile properties, myofibrillar protein content and myosin heavy chain isoforms. RESULTS: Animals treated with 5 mg kg-1 chlorpyrifos had a decrease body weight. An increase by 28% and 24% in latency time assessed by beam walking test and a decrease by 9% and 13% in the beam balance time was reported after 6 weeks of 1 and 5 chlorpyrifos exposure respectively. The contractile properties in soleus showed an increase in twitch amplitude by 25% and 63% in 1 and 5 doses respectively, without modification in the contraction time and half relaxation time. edl treated with 1 mg kg-1 showed a decrease by 35%, 42% and 22% in twitch amplitude, contraction time and half relaxation time respectively. edl treated with 5 mg kg-1 showed an increase of 23% in twitch amplitude without modification of the other parameters. These changes were associated with modification of myofibrillar protein content in all treated groups. Myosin heavy chain isoforms were altered in both skeletal muscles treated with 1 mg kg-1. CONCLUSION: Exposure to chlorpyrifos can alter the locomotion and produce physiological changes in a dose and muscle type related manner.

Effects of selenium supplementation on lung oxidative stress after exposure to exhaust emissions from pyrolysis oil, biodiesel and diesel.

The exposure to exhaust emissions from fuels as diesel and pyrolysis oil may result in adverse effects on human lungs. This study investigated the effects of exposing mice to the exhaust emissions from diesel, biodiesel or pyrolysis oil, for 1 hour/day for 3 days, on lung oxidative stress and whether selenium administration into these mice affects the oxidative stress. The levels of lung malondialdehyde and nitric oxide were increased after exposure to pyrolysis oil exhaust. The intraperitoneal injection of 1.78 µg selenium/kg body weight 15 minutes before the exposure to the pyrolysis oil exhaust (pyrolysis oil + selenium group) restored the normal levels of malondialdehyde and nitric oxide. The catalase and SOD activities were decreased in the groups of the mice exposed to the exhaust emissions from pyrolysis oil, biodiesel or diesel. Selenium pretreatment of these groups showed no significant change in the activities of both enzymes. In conclusion, the increased lung levels of malondialdehyde and nitric oxide after the exposure to the exhaust emission from pyrolysis oil were restored to normal by selenium administration.

Photoswitchable and pH responsive organoplatinum(ii) complexes with azopyridine ligands.

Several platinum(ii) complexes with ligands containing azo groups have been prepared and structurally characterised, and their photoswitching between trans and cis azo group isomers has been studied. The azo groups in the cationic complexes [PtMe(bipy)(4-NC5H4-N[double bond, length as m-dash]N-4-C6H4X)][PF6], X = H, OH or NMe2, and in the dicationic complex [Pt(bipy)(4-H2NC6H4-N[double bond, length as m-dash]N-C6H5)2][OTf]2 undergo trans to cis photoswitching on irradiation at 365 nm. The complex [PtMe(bipy)(4-NC5H4-N[double bond, length as m-dash]N-4-C6H4NMe)2][PF6] also exhibits a reversible halochromic effect on protonation to give the dicationic complex [PtMe(bipy)(4-NC5H4-NH[double bond, length as m-dash]N-4-C6H4NMe2]2+. The nature of the frontier orbitals in the platinum(ii) complexes depends on the charge on the complex and on the degree of metal-ligand π-bonding.

The Protective Effect of Selenium on Oxidative Stress Induced by Waterpipe (Narghile) Smoke in Lungs and Liver of Mice.

Waterpipe smoking is common in the Middle East populations and results in health problems. In this study, we investigated the effects of exposure of mice to waterpipe smoke on oxidative stress in lungs and liver and the effects of selenium administration before smoke exposure on the oxidative stress. Twenty-four mice were divided equally into four groups: (i) the control mice received no exposure or treatment; (ii) mice exposed to waterpipe smoke; (iii) mice received intraperitoneal injection of 0.59 µg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke; and (iv) mice received intraperitoneal injection of 1.78 µg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke. Mice were exposed to waterpipe smoke every other day for four times within 8 successive days. Malondialdehyde and nitric oxide levels were significantly higher in the lungs and liver, while the activities of superoxide dismutase, glutathione peroxidase-1, and catalase were significantly lower in the waterpipe smoke group when compared to control mice. Treating mice with 1.78 µg selenium/kg body weight significantly restored the normal levels of these parameters. Histological examinations of lungs and liver confirmed the protective actions of selenium against the effects of exposure to waterpipe smoke. In conclusion, exposure of mice to waterpipe smoke-induced oxidative stress in lungs and liver. Administration of low level of selenium, 1.78 µg selenium/kg body weight as sodium selenite, exerted protective effects against oxidative stress induced by exposure to waterpipe smoke.

Effects of exendin-4 and selenium on the expression of GLP-1R, IRS-1, and preproinsulin in the pancreas of diabetic rats.

The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 µg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.

A biomimetic phenol substituent effect on the reaction of a dimethylplatinum(ii) complex with oxygen: proton coupled electron transfer and multiple proton relay.

The complex [PtMe2({κ(2)-N,N-RN[double bond, length as m-dash]CH-2-C5H4N})] reacts with oxygen in acetone solution to give the platinum(iv) complex [Pt(OH)Me2{κ(3)-N,N,O-RNH-CH(2-C5H4N)(CH[double bond, length as m-dash]CMeO)}], when R = 2-C6H4OH, but not when R = Ph. It has been suggested that the phenol substituent plays two key biomimetic roles; firstly, in proton coupled electron transfer reactions in the activation of oxygen and hydroperoxide groups and, secondly, in proton relay from a methyl group of the coordinated acetone.

(E)-tert-Butyl 2-(5-{[4-(dimethylamino)phenyl]diazenyl}-2,6-dioxo-1H-pyrimid-in-3-yl)acetate dichloromethane monosolvate.

In the title compound, C18H23N5O4·CH2Cl2, the di-chloro-methane solvent mol-ecule is disordered over two sets of sites in a 0.630 (13):0.370 (13) ratio. The dihedral angle between the uracil and phenyl rings is 30.2 (1)°. In the crystal, the principal inter-actions are N-H⋯O hydrogen bonds, which link uracil units across centres of symmetry, forming eight-membered rings with an R (2) 2(8) graph-set motif. The structure also displays C-H⋯O and C-H⋯Cl hydrogen bonds. Intra-molecular C-H⋯O short contacts are also observed.

Selenium and selenoprotein deficiencies induce widespread pyogranuloma formation in mice, while high levels of dietary selenium decrease liver tumor size driven by TGFα.

Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (Trsp(tG37) ) and/or a cancer driver TGFα transgene. The use of Trsp(tG37) altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. Trsp(tG37) transgenic and TGFα/Trsp(tG37) bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα-induced liver tumors.

Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats.

Selenium and exendin-4 exert antidiabetic effects by unknown mechanisms. Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. Diabetic rats were injected intraperitoneally with exendin-4 (0.03 µg/kg body weight) twice daily or treated with 5 ppm selenium as sodium selenite in drinking water for 4 weeks. Both selenium and exendin-4 reduced the hyperglycemia in diabetic rats. Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver.

A bioinformatics approach to characterize mammalian selenoprotein T.

The exact function and trafficking of selenoprotein T (SelT) are still unclear. This study was focused on using bioinformatics analysis as an approach to understanding the structure-function relationship of SelT and the trafficking of SelT between cellular compartments. Blast analysis revealed that SelT is present in mammals, birds, frogs, zebra fish, and green algae. Structural analyses revealed that SelT contains a CxxU motif in a thioredoxin-like fold, suggesting a redox function of SelT. Cysteine (Cys) residues were found in the place of selenocysteine in SelT Cys homologs in insects, roundworms, and plants. The SignalP program recognized signal peptides in both SelT and SelT Cys homologs. Mammalian SelT was predicted to contain an N-terminal signal peptide of 19 amino acid residues, which may be involved in targeting SelT to the endoplasmic reticulum. Finally, SelT may be localized in the plasma membrane in addition to its presence in the Golgi apparatus and the endoplasmic reticulum.

An azo-based PNA monomer: synthesis and spectroscopic study.

The full synthetic details and photospectroscopic characterization of a peptide nucleic acid (PNA) monomer suitable for Fmoc-based oligomerization chemistry that bears an azobenzene moiety as a base surrogate are reported. The monomer showed the ability to quench the fluorescence emission of fluorescein and pyrene luminophores and proved to be a competent Föster resonance energy transfer partner in a PNA-based molecular beacon.

Regulation of selenoproteins and methionine sulfoxide reductases A and B1 by age, calorie restriction, and dietary selenium in mice.

Methionine residues are susceptible to oxidation, but this damage may be reversed by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the major methionine sulfoxide reductase in liver of mice and it is among the proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA activities, were reduced with age, and the selenium regulation of MsrB1 was preserved in the aging liver, suggesting that MsrB1 could account for the impaired methionine sulfoxide reduction in aging animals. We also examined regulation of Msr and selenoprotein expression by a combination of dietary selenium and calorie restriction and found that, under calorie restriction conditions, selenium regulation was preserved. In addition, mice overexpressing a mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed in selenium deficiency, whereas MsrA activity was elevated in these animals. Finally, we show that selenium regulation in inbred mouse strains is preserved in an outbred aging model. Taken together, these findings better define dietary regulation of methionine sulfoxide reduction and selenoprotein expression in mice with regard to age, calorie restriction, dietary Se, and a combination of these factors.

Selective restoration of the selenoprotein population in a mouse hepatocyte selenoproteinless background with different mutant selenocysteine tRNAs lacking Um34.

Novel mouse models were developed in which the hepatic selenoprotein population was targeted for removal by disrupting the selenocysteine (Sec) tRNA([Ser]Sec) gene (trsp), and selenoprotein expression was then restored by introducing wild type or mutant trsp transgenes. The selenoprotein population was partially replaced in liver with mutant transgenes encoding mutations at either position 34 (34T-->A) or 37 (37A-->G) in tRNA([Ser]Sec). The A34 transgene product lacked the highly modified 5-methoxycarbonylmethyl-2'-O-methyluridine, and its mutant base A was converted to I34. The G37 transgene product lacked the highly modified N(6)-isopentenyladenosine. Both mutant tRNAs lacked the 2'-methylribose at position 34 (Um34), and both supported expression of housekeeping selenoproteins (e.g. thioredoxin reductase 1) in liver but not stress-related proteins (e.g. glutathione peroxidase 1). Thus, Um34 is responsible for synthesis of a select group of selenoproteins rather than the entire selenoprotein population. The ICA anticodon in the A34 mutant tRNA decoded Cys codons, UGU and UGC, as well as the Sec codon, UGA. However, metabolic labeling of A34 transgenic mice with (75)Se revealed that selenoproteins incorporated the label from the A34 mutant tRNA, whereas other proteins did not. These results suggest that the A34 mutant tRNA did not randomly insert Sec in place of Cys, but specifically targeted selected selenoproteins. High copy numbers of A34 transgene, but not G37 transgene, were not tolerated in the absence of wild type trsp, further suggesting insertion of Sec in place of Cys in selenoproteins.

Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice.

The micronutrient element selenium (Se) has been shown to be effective in reducing the incidence of cancer in animal models and human clinical trials. Selenoproteins and low molecular weight Se compounds were implicated in the chemopreventive effect, but specific mechanisms are not clear. We examined the role of Se and selenoproteins in liver tumor formation in TGFalpha/c-Myc transgenic mice, which are characterized by disrupted redox homeostasis and develop liver cancer by 6 months of age. In these mice, both Se deficiency and high levels of Se compounds suppressed hepatocarcinogenesis. In addition, both treatments induced expression of detoxification genes, increased apoptosis and inhibited cell proliferation. Within low-to-optimal levels of dietary Se, tumor formation correlated with expression of most selenoproteins. These data suggest that changes in selenoprotein expression may either suppress or promote tumorigenesis depending on cell type and genotype. Since dietary Se may have opposing effects on cancer, it is important to identify the subjects who will benefit from Se supplementation as well as those who will not.

Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation.

Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.

Chimerism and tolerance post-in utero transplantation with embryonic stem cells.

BACKGROUND: Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. METHODS: MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kd) at 1 x 10(9) cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity< or =0.1%) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 x 10(9) of the corresponding cells/kg body weight. RESULTS: After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0% to 0.4%. PB with 1 x 10(9)/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0% within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. CONCLUSIONS: Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.

Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P < 0.05) before ablation, perhaps accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.