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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 x DBA/2) F1J revealed influences of genetic factors on life span. Females lived longer than males. Dilute brown females died sooner than females of other colors. H-2b/H-2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that male and female genotypes each fall into two groups, with female dilute brown mice having shorter lives than other females, and male H-2b/H-2b mice except dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other males. The association of heterozygosity with life span was clearer in females than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H-2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H-2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings at postmortem differed between the sexes, there was no association of particular disorders with other genetic markers. The importance of H-2 in males was confirmed, but the allelic effects were perturbed, possibly by the absence of Sendai infection in this experiment. Overall our studies suggest that genetic influences on life span involve interactions between loci, and allelic interactions may change with viral infections or other environmental factors.
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PMID:Traits that influence longevity in mice: a second look. 139 56

Clonogenic assays for M, GM, and G precursors of rat or mouse marrow cells were performed in the presence of medium conditioned by the growth of ASL-1 leukemia X LM fibroblast hybrid cells. Both GM- and M-colony-forming units (CFUs) were present in marrow cultures maintained in conditioned medium (CM) from hybrid cells (up to 162 +/- 10 total colonies per 10(5) cells) and from LM cells (65 +/- 5). Conditioned medium from ASL-1 cells did not lead to the formation of CFUs. The hybrid cell-derived CM supported the development of M and GM-CFUs from the marrows of DBA, CAF1, BDF1, C3D2F1, and C57B1/6 mice as well as Lewis, Brown Norway, and Wistar Furth rats. G-CFU were not detected in any of the preparations. Hybrid cell-CM supported the long-term growth and proliferation of macrophage-like cells from mouse spleen, consistent with the presence of M-colony-stimulating factor (CSF). Evidence that M-CSF formed by the hybrid cells and M-CSF formed by L cells shared structural features was provided by antibody neutralization studies. The CFU-promoting activity of hybrid cell-derived M-CSF was neutralized by an antiserum raised in goats against M-CSF purified from L cells. Independently prepared ASL-1 X LM hybrid cells, like the original, led to the formation of GM and M-CFUs. Attempts to detect each of several other previously defined growth factors in medium conditioned by the hybrid cells were unsuccessful. Interleukins 1, 2, and 3; B cell growth factors interferons alpha, beta, and gamma; erythropoietin; and burst promoting factor were not detected.
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PMID:Formation of macrophage (M) colony-stimulating factor by murine leukemia x fibroblast hybrid cells. 349 13

A carcinogen binding protein (CBP) that is implicated in controlling the expression of rat cytochrome P-450c which is closely associated with aryl hydrocarbon hydroxylase (AHH) was examined in hepatic and extrahepatic tissues of the neonatal and adult New Zealand White (NZW) rabbits, the hepatic tissue of the BALB/cJ and DBA/2J mice, Brown Norway rat, Golden Syrian hamster and Hartley guinea pig. These animals and tissues were examined in order to determine whether there was a correlation of CBP levels and the reported presence or absence of inducibility of AHH in these tissues. The CBP was found in hepatic and extrahepatic tissue of the NZW rabbit and the hepatic tissues of all animals except the Hartley guinea pig. The Hartley guinea pig may provide a useful animal with which to further examine the role of CBP in cytochrome induction. Since the CBP is not a tissue specific protein and because it is found in both neonatal and adult NZW rabbit tissue, the data suggests that the CBP is not the limiting factor in the tissue specific induction of cytochromes nor in developmentally controlled induction of cytochromes previously reported in the rabbit.
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PMID:Species and tissue distribution of the 4S carcinogen binding protein and its possible role in cytochrome P-450 induction. 358 Dec 84

Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat. We report here the use of molecular genetic linkage analysis to test the hypothesis that fa is a mutant allele of the CRF gene. A restriction fragment length polymorphism for CRF between Zucker (13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty mutation should be homozygous for the 13M CRF allele. However, only 10/58 fa/fa animals were homozygous for the 13M CRF allele, indicating that fa and CRF are not allelic. Thus, although CRF may be important in the physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II (Car-2) gene on mouse chromosome 3, in a region of synteny-homology with rat chromosome 2. Thus the rat CRF gene is probably located on chromosome 2.
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PMID:The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor. 843 Aug 72

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.
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PMID:Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice. 902 Dec 2

Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner. Gabapentin at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The potentiation induced by gabapentin was greatest for diazepam, phenobarbital and valproate, less for felbamate and phenytoin and least for carbamazepine and lamotrigine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of the above drugs + gabapentin was more favourable than that of the same drugs + saline. Since gabapentin did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that gabapentin can modify the clearance from the brain of the anticonvulsant drugs studied can not be excluded. In addition, gabapentin did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, gabapentin showed an additive effect when administered in combination with certain classical anticonvulsants, most notably diazepam, phenobarbital, felbamate, phenytoin and valproate.
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PMID:Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. 967 Oct 96

The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging in rodents in order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57BI/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals were shipped to offsite NIA investigators internationally, with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life span, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms.
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PMID:Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. 1061 12

The purpose of this study was to determine: (1) which of the commonly used strains of laboratory rats and mice provide good models for human age-related cataract, and (2) whether long term caloric restriction, a regimen that prolongs both median and maximum life span in rodents, would also delay the time of appearance of this age-related pathology. Three strains of mice and two rat strains commonly used in laboratory work and maintained on either ad libitum (AL) or calorically restricted (CR) diets in the National Institutes of Aging and Diet Restriction colony were examined by slit lamp for age-related cataracts at four or more time points during their life spans. These strains were Brown Norway and Fischer 344 rats, and C57BL/6, (C57BL6 x DBA/2)F1 and (C57BL/6 x C3H)F1 mice. None of these strains develop congenital cataracts. Various stages of cataract were found in the great majority of these animals in old age. In both rat strains and one mouse strain the cataracts occurred after mid-life, were most advanced late in life, and were similar in locations and appearance to those in humans. In the two mouse strains in which some cataracts appeared as early as 10-14 months of age, previously identified genetic defects affecting the eye were probably involved in the early appearances. CR extended life spain in all five rat and mouse strains and also delayed both the time of first appearances and the subsequent increase in cataract severity over time in the four dark-eyed strains. CR did not delay cataract formation in the single albino rat strain studied. In summation: (1) commonly used strains of laboratory rats and mice that are free of congenital or early appearing cataracts due to genetic defects would appear to serve as appropriate models for human age-related cataract, (2) caloric restriction (CR) provides a protective effect, delaying development of cataracts in the dark-eyed mouse and rat strains, while also extending their life spans, (3) CR did not delay the development of lens damage in the nonpigmented eye of the single albino strain studied, although it extended life span.
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PMID:Normal mouse and rat strains as models for age-related cataract and the effect of caloric restriction on its development. 1087 May 27

Hindlimb pain models developed in rats have been transposed to mice, but assumed sciatic nerve neuroanatomic similarities have not been examined. We compared sciatic nerve structural organization in mouse strains (C57BL/6J, DBA/2J, and B6129PF2/J) and rat strains (Wistar, Brown Norway, and Sprague-Dawley). Dissection and retrograde labeling showed mouse sciatic nerve origins predominantly from the third lumbar (L3) and L4 spinal nerves, unlike the L4 and L5 in rats. Proportionate contributions by each level differed significantly between strains in both mice and rats. Whereas all rats had six lumbar vertebrae, variable patterns in mice included mostly five vertebrae in DBA/2J, mostly six vertebrae in C57BL/6J, and a mix in B6129PF2/J. Mice with a short lumbar vertebral column showed a rostral shift in relative contributions to the sciatic nerve by L3 and L4. Ligation of the mouse L4 nerve created hyperalgesia similar to that in rats after L5 ligation, and motor changes were similar after mouse L4 and rat L5 ligation (foot cupping) and after mouse L3 and rat L4 ligation (flexion weakness). Thus, mouse L3 and L4 neural segments are anatomically and functionally homologous with rat L4 and L5 segments. Neuronal changes after distal injury or inflammation should be sought in the mouse L3 and L4 ganglia, and the spinal nerve ligation model in mice should involve ligation of the L4 nerve while L3 remains intact. Strain-dependent variability in segmental contributions to the sciatic nerve may account in part for genetic differences in pain behavior after spinal nerve ligation.
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PMID:Species and strain differences in rodent sciatic nerve anatomy: implications for studies of neuropathic pain. 1831 60

We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.
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PMID:Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants. 2113 62


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