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Strain-specific Differences (strain-specific + difference)
Selected AbstractsMOUSE STRAIN-SPECIFIC DIFFERENCES IN CARDIAC METABOLIC ENZYME ACTIVITIES OBSERVED IN A MODEL OF ISOPROTERENOL-INDUCED CARDIAC HYPERTROPHYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2007Michael D Faulx SUMMARY 1Alterations in myocardial energy metabolism accompany pressure overload-induced hypertrophy. We previously described a novel model of catecholamine-induced hypertrophy in which A/J mice exhibit more robust cardiac hypertrophy than B6 mice. Accordingly, we assessed the influence of mouse strain on the activities of key myocardial metabolic enzymes and whether there are strain-related metabolic adaptations to short-term, high-dose isoproterenol (ISO) administration. 2Thirty-nine male mice (19 A/J mice, 20 B6 mice), aged 12,15 weeks, were randomly assigned to receive either ISO (100 mg/kg, s.c.) or vehicle (sterile water) daily for 5 days. On Day 6, all hearts were excised, weighed, freeze clamped and assayed for pyruvate dehydrogenase (PDH), medium chain acyl-CoA dehydrogenase, carnitine palmitoyl transferase I and citrate synthase activities. Plasma fatty acids (FA) were also measured. 3The ISO-treated A/J mice demonstrated greater percentage increases in gravimetric heart weight/bodyweight ratio than ISO-treated B6 mice (24 vs 3%, respectively; P < 0.001). All enzyme activities were significantly greater in vehicle-treated B6 mice than in A/J mice, illustrating a greater capacity for aerobic metabolism in B6 mice. Administration of ISO reduced PDHa (active form) activity in B6 mice by 47% (P < 0.001), with no significant change seen in A/J mice. Free FA levels were not significantly different between groups; thus, the differences in PDHa were not due to changes in FA. 4The basal activity of myocardial metabolic enzymes is greater in B6 mice than in A/J mice and ISO alters myocardial PDH activity in a mouse strain-dependent manner. Compared with A/J mice, B6 mice demonstrate less ISO-induced cardiac hypertrophy, but greater activity of key enzymes regulating FA and carbohydrate oxidation, which may protect against the development of hypertrophy. The metabolic adaptations associated with ISO-induced hypertrophy differ from those reported with pressure overload hypertrophy. [source] Gender-specific polygenic control of ethylnitrosourea-induced oncogenesis in the rat peripheral nervous systemINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Bernd U. Koelsch Abstract The inbred BD rat strains constitute a model system for analysis of the genetic basis of susceptibility or resistance to the development of neural tumors, as they exhibit distinct strain-specific differences regarding the sensitivity to tumor induction by the alkylating carcinogen N -ethyl- N -nitrosourea (EtNU). Among the different BD strains, BDIX and BDIV rats, respectively, are either highly susceptible or entirely resistant to the development of EtNU-induced malignant schwannomas of the peripheral nervous system (PNS), predominantly of the trigeminal nerves. We have previously mapped one locus associated with susceptibility/resistance to schwannoma induction to the telomeric third of chromosome 10 (Mss1) in segregating (BDIX × BDIV) crosses. We report on the genetic mapping of 6 further loci controlling tumor incidence or survival time on chromosomes 1 (Mss2), 3 (Mss3), 6 (Mss4), 13 (Mss5) and 15 (Mss6) as well as on chromosome 10 (Mss7) close to the centromere. Interestingly, most of these loci mediate gender-specific effects of variable strength ranging from minor influences on tumor development to complete tumor resistance. The gender specificity is reflected by the fact that male (BDIX × BDIV) F2 rats exhibit a 2-fold higher incidence of EtNU-induced schwannomas than females as well as a shorter survival time. A number of human nervous system tumors too arise with a marked gender bias. Genes mediating gender-specific predisposition of developing malignant schwannomas in the rat may be relevant for the human individual risk of developing nervous system tumors. © 2005 Wiley-Liss, Inc. [source] Genetically Based Influences on the Site-Specific Regulation of Trabecular and Cortical Bone Morphology,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Stefan Judex Abstract The degree of site-specificity by which genes influence bone quantity and architecture was investigated in the femur of three strains of mice. Morphological indices were highly dependent on both genetic makeup as well as anatomical location showing that the assessment of bone structure from a single site cannot be extrapolated to other sites even within a single bone. Introduction: The identification of genes responsible for establishing peak BMD will yield critical information on the regulation of bone quantity and quality. Whereas such knowledge may eventually uncover novel molecular drug targets or enable the identification of individuals at risk of osteoporosis, the site-specificity by which putative genotypes cause low or high bone mass (and effective bone morphology) is essentially unknown. Materials and Methods: ,CT was used to determine morphological and microarchitectural features of the femora harvested from three genetically distinct strains of 4-month-old female mice, each with distinct skeletal mass (low: C57BL/6J [B6], medium: BALB/cByJ [BALB], high: C3H/HeJ [C3H]). Two trabecular regions (distal epiphysis and metaphysis) were considered in addition to four cortical regions within the metaphysis and diaphysis. Results and Conclusions: Comparing morphological properties of the different trabecular and cortical femoral regions between the three strains of mice, it was apparent that high or low values of specific parameters of bone morphology could not be consistently attributed to the same genetic strain. Trabecular metaphyseal bone volume, for instance, was 385% larger in C3H mice than in B6 mice, yet the two strains displayed similar bone volume fractions in the epiphysis. Similarly, BALB mice had 48% more trabecular bone than C3H mice in the epiphysis, but there were no strain-specific differences in cortical bone area at the diaphysis. These data suggest that the genetic control of bone mass and morphology, even within a given bone, is highly site-specific and that a comprehensive search for genes that are indicative of bone quantity and quality may also have to occur on a very site-specific basis. [source] Transcriptome analysis of Listeria monocytogenes identifies three groups of genes differently regulated by PrfAMOLECULAR MICROBIOLOGY, Issue 6 2003Eliane Milohanic Summary PrfA is the major regulator of Listeria virulence gene expression. This protein is a member of the Crp/Fnr family of transcription regulators. To gain a deeper understanding of the PrfA regulon, we constructed a whole-genome array based on the complete genome sequence of Listeria monocytogenes strain EGDe and evaluated the expression profiles of the wild-type EGDe and a prfA -deleted mutant (EGDe ,prfA). Both strains were grown at 37°C in brain,heart infusion broth (BHI) and BHI supplemented with either activated charcoal, a compound known to enhance virulence gene expression, or cellobiose, a sugar reported to downregulate virulence gene expression in spite of full expression of PrfA. We identified three groups of genes that are regulated differently. Group I comprises, in addition to the 10 already known genes, two new genes, lmo2219 and lmo0788, both positively regulated and preceded by a putative PrfA box. Group II comprises eight negatively regulated genes: lmo0278 is preceded by a putative PrfA box, and the remaining seven genes (lmo0178,lmo0184) are organized in an operon. Group III comprises 53 genes, of which only two (lmo0596 and lmo2067) are preceded by a putative PrfA box. Charcoal addition induced upregulation of group I genes but abolished regulation by PrfA of most group III genes. In the presence of cellobiose, all the group I genes were downregulated, whereas group III genes remained fully activated. Group II genes were repressed in all conditions tested. A comparison of the expression profiles between a second L. monocytogenes strain (P14), its spontaneous mutant expressing a constitutively active PrfA variant (P14prfA*) and its corresponding prfA -deleted mutant (P14,prfA) and the EGDe strain revealed interesting strain-specific differences. Sequences strongly similar to a sigma B-dependent promoter were identified upstream of 22 group III genes. These results suggest that PrfA positively regulates a core set of 12 genes preceded by a PrfA box and probably expressed from a sigma A-dependent promoter. In contrast, a second set of PrfA-regulated genes lack a PrfA box and are expressed from a sigma B-dependent promoter. This study reveals that PrfA can act as an activator or a repressor and suggests that PrfA may directly or indirectly activate different sets of genes in association with different sigma factors. [source] | ||||||||||