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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inbred mouse strains vary in sensitivity to a number of behavioral and physiological effects produced by nicotine. Differences in sensitivity to nicotine are correlated with variance in the number of brain nicotinic receptors as measured in regionally dissected brain tissue. The studies reported here used quantitative autoradiography and in-situ hybridization methods to measure regional levels of alpha-bungarotoxin (alpha BTX) binding and alpha 7 mRNA levels. Two inbred mouse strains, ST/b and DBA/2, were compared because these strains differ maximally in sensitivity to nicotine-induced seizures and in alpha BTX binding measured in regional brain homogenates. The binding of alpha BTX was significantly greater in the St/b strain in 42 of 127 brain regions that were analyzed, and a trend towards increased binding was seen in many additional brain regions. The most consistent strain differences were found in hippocampal, thalamic and pontine nuclei. Strain differences in alpha 7 mRNA levels were also detected, but these were not as widespread as were the alpha BTX binding differences. The alpha 7 mRNA levels were significantly correlated with alpha BTX binding in both mouse strains which suggests that the strain differences in binding are related, in part, to the levels of alpha 7 mRNA.
Brain Res Mol Brain Res 1996 Jul
PMID:ST/b and DBA/2 mice differ in brain alpha-bungarotoxin binding and alpha 7 nicotinic receptor subunit mRNA levels: a quantitative autoradiographic analysis. 880 29

The anti-cancer activity of dimers joined with ether, ester or carbon-carbon bonds by photodynamic therapy (PDT) was compared by using DBA/2 mice transplanted with SMT/F tumors. Dimers with ether and carbon-carbon linkages were found to be more effective than those linked with ester bonds. Variation of the substituents at peripheral positions made a significant difference in in vivo efficacy. Among the ether and carbon-carbon linked dimers, the divinyl analogs were found to be most effective. The preliminary in vivo results also suggest that the position(s) of the hydrophilic substituents in the molecules make a remarkable difference in photosensitizing activity. An unsymmetrical dimer with an amide linkage, obtained from 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) was found to be less effective than HPPH.
J Mol Recognit
PMID:Comparative in vivo sensitizing efficacy of porphyrin and chlorin dimers joined with ester, ether, carbon-carbon or amide bonds. 887 2

TCDD, endrin and lindane induce an oxidative stress and enhance lipid peroxidation in fetal and placental tissues of mice. The levels of the products resulting from altered lipid metabolism, including malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) have been determined in maternal sera and amniotic fluids of pregnant C57BL/6J and DBA/2J mice after oral administration of single fetotoxic doses of TCDD, endrin and lindane on day 12 of gestation, using high pressure liquid chromatography (HPLC). Under these conditions, TCDD given at a dose of 30 micrograms/kg body weight to C57BL/6J mice produced 2.5-3.9 and 1.7-4.0 fold increases in the levels of the four metabolites in maternal sera and the amniotic fluids, respectively. TCDD given to DBA/2J mice at a dose of 60 micrograms/kg produced 1.5-1.7 and 1.7-2.2 fold increases in the levels of these metabolites in maternal sera and the amniotic fluids, respectively. Endrin, when given at a dose of 4.5 mg/kg body weight to either mouse strain, produced increases of 1.9-3.1 and 1.7-3.2-fold in the levels of the four metabolites in maternal sera and the amniotic fluids, respectively, in the C57BL/6J mice and increases of 1.4-1.6 and 1.2-1.5 fold in the levels of these metabolites in maternal sera and the amniotic fluids, respectively, in the DBA/2J mice. Lindane given at a dose of 30 mg/kg body weight to C57BL/6J mice produced 1.5-2.0 and 1.3-1.7-fold increases in the four metabolites in maternal serum and amniotic fluids, respectively, while administration of this same dose to DBa/2J mice produced 1.2-1.5 and 1.1-1.5 fold increases, respectively. Increases in the levels of lipid metabolites occur in maternal serum and amniotic fluid as a result of enhanced lipid peroxidation in response to TCDD, endrin and lindane. Lipid peroxidation may participate in the fetotoxic effects of these xenobiotics and these effects are observed regardless of the Ah-responsiveness of the mice, although higher levels of the metabolites are produced by TCDD in Ah-responsive mice.
Res Commun Mol Pathol Pharmacol 1996 Nov
PMID:TCDD endrin and lindane induced increases in lipid metabolites in maternal sera and amniotic fluids of pregnant C57BL/6J and DBA/2J mice. 898 13

SCN1B, the human gene encoding the beta1-subunit of the voltage-gated sodium channel has previously been cloned and mapped to Chr 19q13.1. The sequence of the homologous mouse gene, Scn1b, has now been determined from cDNA. The mouse gene is highly conserved, encoding a predicted protein with 99%, 98% and 96% amino acid identity to the rat, rabbit, and human homologs, respectively. DNA sequence conservation is also striking in the 3' untranslated region which shows 67% and 98% to human and rat, respectively. Unlike the human and rat homologs, high expression of mRNA from the mouse gene is confined to adult skeletal muscle and brain, and is not observed in heart. As Scnlb maps to Chr 7, in close genetic proximity to the quivering gene (qv), the coding region of Scnlb was also cloned from a qvJ/qvJ homozygous mouse and assessed as a candidate for the site of this genetic defect. Comparison of qv and wild-type cDNAs showed no changes in the predicted amino acid sequence that could cause the qv phenotype. However, three silent polymorphisms in the DNA coding region indicate that Scn1b is close to qv, and is within a region of genetic identity with DBA/2J, the inbred background on which the qvJ allele arose.
Brain Res Mol Brain Res 1996 Dec
PMID:Sequence of the voltage-gated sodium channel beta1-subunit in wild-type and in quivering mice. 901 77

Inbred mouse strains have been shown to differ in their levels of brain alpha-bungarotoxin binding. These differences in alpha-bungarotoxin receptors have been shown to correlate with an animal's sensitivity to nicotine-induced seizures. Recent studies have shown that the alpha 7 nicotinic acetylcholine receptor subunit is the major alpha-bungarotoxin binding site in rodent brain. In this report, we examined whether mouse strains that differ in levels of alpha-bungarotoxin binding and sensitivity to nicotine-induced convulsions also differ for the alpha 7 subunit. A full-length murine alpha 7 cDNA was cloned and sequenced and found to be identical to that of a mouse alpha 7 cDNA recently reported. Subsequently, a comparison of alpha 7 cDNA sequences and RNA species was performed between two strains (C3H/2 and DBA/2) that differ in levels of brain alpha-bungarotoxin binding and sensitivity to nicotine-induced seizures. The only difference observed was a single nucleotide difference in the open reading frame of alpha 7 that does not affect the primary amino acid sequence. Inbred strains were also surveyed for restriction fragment length polymorphisms at the alpha 7 locus. Strain-specific polymorphisms were identified, and F2 and backcross animals from a classic genetic cross between C3H/2 and DBA/2 mice were compared for the inheritance of alpha 7 genotype and alpha-bungarotoxin receptor levels. A significant association between genotype and receptor levels was observed in both, the F2 and backcross generations. These results indicate that alpha 7 genotype is an important determinant of alpha-bungarotoxin receptor levels.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Linkage of strain-specific nicotinic receptor alpha 7 subunit restriction fragment length polymorphisms with levels of alpha-bungarotoxin binding in brain. 903 16

Monoclonal antibodies anti-SSEA-1 and EMA-1, and the lectins DBA and LTA, bound to the surface of large, round cells randomly distributed in the 26-day pig genital ridge. Other antibodies, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81, did not react with any cells in the pig genital ridge. SSEA-1-positive cells displayed pseudopods and appeared to migrate from the dorsal mesentery of the hindgut (18-day) to the primordium of the gonad (day 23) and entered the genital ridge by 26 days. The number of SSEA-1-positive cells associated with the dorsal mesentery and genital ridge markedly increased from the 18-day to the 26-day pig embryo. It was concluded that the SSEA-1-positive cells were primordial germ cells (PGCs). Using these markers and alkaline phosphatase histochemistry, pig PGCs derived from the 26-day genital ridge showed no proliferation when grown in STO co-culture in the presence of human LIF, bFGF and SCF.
Mol Reprod Dev 1997 Apr
PMID:Identification of pig primordial germ cells by immunocytochemistry and lectin binding. 909 3

To determine the molecular mechanism of regulation of pentylenetetrazol (PTZ)-induced calcium entry by the seizure-related gene, PTZ-17, the role of the 3'-untranslated region (3'UTR) and also interaction between 3'UTR and intracellular factors were investigated. PTZ-induced calcium inward current in Xenopus oocytes injected with PTZ-17 RNA varied in magnitude among strains of mice: RNA derived from the DBA/2 mouse, which has a high susceptibility to convulsions, showed the largest current and that from the BALB/c mouse with a low susceptibility to convulsions showed no PTZ response. The sequence of 3'UTR showed alterations among mouse strains: 3'UTR of BALB/c showed a sequence alteration from T to G and that of DBA/2 showed a GTG insertion compared with that of B6. The 3'UTR also regulated the translation of chloramphenicol acetyltransferase (CAT) RNA depending on its sequence. A particular region within the 3'UTR demonstrated interaction with 60- and 47-kDa proteins. Sequence alterations in this region corresponded to disappearance or increase in PTZ-induced calcium entry. These findings suggest that a particular region within 3'UTR of the seizure-related gene, PTZ-17, is involved in PTZ-induced calcium entry via interaction between mRNA and specific RNA-binding proteins.
Brain Res Mol Brain Res 1997 Jul
PMID:Molecular mechanism of regulation of pentylenetetrazol-induced calcium entry by 3'-untranslated region of a seizure-related cDNA, PTZ-17, in Xenopus oocytes. 922 1

The regulation of CYP1A1 and CYP1A2 isozymes by piperonyl butoxide (PBO) and acenaphthylene (ACN) was studied in the liver of male C57BL/6 and DBA/2 mice. These two cytochrome P450 genes are known to be regulated by the aromatic hydrocarbon-responsive receptor (AHR); however, it has been suggested that CYP1A2 is also induced by an AHR-independent mechanism. In this study, PBO induced hepatic CYP1A1 considerably more in C57BL/6 (Ahrb-I) than in DBA/2 (Ahrd) mice. In addition, the superinduction of CYP1A1 in wildtype hepa1c1c7 cells, which is AHR-dependent, resulted from PBO and cycloheximide treatment of the cells. In other studies in this laboratory using AHR knock-out (AHR-/-) mice, a hybrid of 129/SV and C57BL/6 strains, no induction of CYP1A1 occurred with PBO or ACN. [D.-Y. Ryu, P.E. Levi, P. Fernandez-Salguero, F.J. Gonzalez, E. Hodgson, Mol. Pharmacol., 50 (1996) 443-446.] ACN, however, did not induce CYP1A1 under the experimental conditions used. These results suggest that PBO, but not ACN, induces CYP1A1 through a weak activation of AHR. On the other hand, hepatic CYP1A2 mRNA and hnRNA were induced by PBO in both C57BL/6 and DBA/2 strains, but were not induced by ACN, a strong inducer of CYP1A2 in the B6C3F1 strain. However, both PBO and ACN induced CYP1A2 in AHR-/- mice. It is assumed, therefore, that the transcriptional induction of CYP1A2 by PBO and ACN is AHR-independent. In addition, the induction of CYP1A2 by ACN depends upon the strain of mice. Immunohistochemical studies for CYP1A1/CYP1A2 apoproteins showed that PBO induced CYP1A1/CYP1A2 around the central veins as did 3-methylcholanthrene (3-MC). The induction of CYP1A1/CYP1A2 by ACN, however, was not observed, consistent with the northern blot results.
 ...
PMID:Regulation of hepatic CYP1A isozymes by piperonyl butoxide and acenaphthylene in the mouse. 923 75

It has been known for many years that there are dramatic differences in the susceptibility of mouse stocks and strains to two-stage skin carcinogenesis and that these differences are due the animals' responsiveness to tumor-promoting agents. In earlier studies using several inbred mouse strains, we found that susceptibility to skin tumor promotion by phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) is a multigenic trait. To extend this work, we conducted a genome scan of (C57BL/6 x DBA/2)F1 x C57BL/6 mice previously scored for sensitivity to skin tumor promotion by TPA. As a result of this scan, we now report an association of increased TPA promotion susceptibility with inheritance of the DBA/2 alleles of markers on the distal portion of mouse chromosome 9. Additional linkage analyses using (C57BL/6 x DBA/2)F2 and B x D recombinant inbred mice confirmed this association and suggested that a TPA promotion susceptibility locus maps near D9Mit51 (LODw = 4.1). We designated this locus promotion susceptibility locus 1 (Ps/1).
Mol Carcinog 1997 Oct
PMID:Association of a murine chromosome 9 locus (Psl1) with susceptibility to mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 936 5

The binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the aryl hydrocarbon (AH) receptor and subsequent changes in gene expression have been studied intensively, but the mechanisms by which these lead to toxicity are unclear. We investigated the influence of iron, previously implicated in TCDD-induced hepatic porphyria, in mice with alleles of Ahr that encode receptors with varied affinity for TCDD. The administration of iron to Ahrb-1 C57BL/6J (AH-responsive) mice before a single dose of TCDD (75 micrograms/kg) markedly potentiated not only the hepatic porphyria but also general hepatocellular damage and elevation of plasma hepatic enzymes. The formation of hydroxylated and peroxylated derivatives of uroporphyrins formed from uroporphyrinogen and the induction of a mu-glutathione transferase (GST) were consistent with the operation of an oxidative mechanism. In a comparison of C57BL/6J mice with Ahrb-2 BALB/c (AH-responsive) and Ahrd SWR and DBA/2 (AH-nonresponsive) mice, iron overcame the weak hepatic porphyria and toxicity responses in BALB/c and SWR strains but not in DBA/2. CYP1A isoforms are strongly implicated in the mechanism of porphyria, but activities were lowered by 20-30% with iron treatment, and a comparison of levels between strains did not fully account for the resistance of DBA/2 mice. Studies with the use of gel shift assays and cytosolic aconitase of the capacity of the iron regulatory protein controlling the translation of some iron metabolism proteins showed a significant difference between C57BL/6J and DBA/2 mice after the administration of TCDD. We conclude that iron potentiates both the hepatic porphyria and toxicity of TCDD in susceptible mice in an oxidative process with disturbance of iron regulatory protein capacity. Iron even overcomes the AH-nonresponsive Ahrd allele in the SWR strain but not in DBA/2 mice, which remain resistant.
Mol Pharmacol 1998 Jan
PMID:Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism. 944 32


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