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Different Genetic Backgrounds (different + genetic_background)
Selected AbstractsPedigree analysis in the Austrian Noriker draught horse: genetic diversity and the impact of breeding for coat colour on population structureJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 5 2009T. Druml Summary The pedigree of the current Austrian Noriker draught horse population comprising 2808 horses was traced back to the animals considered as founders of this breed. In total, the number of founders was 1991, the maximum pedigree length was 31 generations, with an average of 12.3 complete generations. Population structure in this autochthonous Austrian draught horse breed is defined by seven breeding regions (Carinthia, Lower Austria, Salzburg, Styria, Tyrol, Upper Austria and Vorarlberg) or through six coat colour groups (Bay, Black, Chestnut, Roan, Leopard, Tobiano). Average inbreeding coefficients within the breeding regions ranged from 4.5% to 5.5%; for the colour groups, the coefficients varied from 3.5% to 5.9%. Other measures of genetic variability like the effective number of founders, ancestors and founder genomes revealed a slightly different genetic background of the subpopulations. Average coancestries between and within breeding areas showed that the Salzburg population may be considered as the nucleus or original stock whereas all other subpopulations showed high relationship to horses from Salzburg. The target of draught horse breeding in the 21st century does not meet the breeding concept of maximizing genetic gains any more. Stabilizing selection takes place. In this study, we show that demographic factors as well as structure given by different coat colours helped to maintain genetic diversity in this endangered horse breed. [source] Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Anna Solovey Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low-TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L -NAME (N -nitro- L -arginine-methyl-ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high-TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOS-Tg) or to have an eNOS knockout state (one eNOS,/, animal and several eNOS+/, animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down-regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Induction of Intestinal Tumors and Lymphomas in C57BL/6N Mice by a Food-borne Carcinogen, 2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridineCANCER SCIENCE, Issue 5 2002Masako Ochiai 2-Amino-l-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is the most abundant heterocyclic amine contained in cooked meat and fish. Although PhIP has been demonstrated to induce various types of tumors in rats, lymphomas predominated in mice using the CDF1 strain. To investigate the carcinogenic activity of PhIP on other organs in mice with a different genetic background, PhIP was administered to C57BL/6N mice. After a 40-week administration of 300 ppm of PhIP in a high-fat diet followed by continuous feeding with a high fat diet, C57BL/6N mice developed adenomas and adenocarcinomas in the small intestine, the incidences being 52% in males and 68% in females at weeks 95 and 70, respectively. Lymphomas of B-cell origin also developed in both sexes as frequently as in the CDF1 strain, incidences being 48% in males and 32% in females. Although the incidence in PhIP-treated female mice did not differ from that in the control mice, lymphomas developed significantly earlier in the PhIP-treated mice. The present study demonstrated that the intestinal tract is another potential target of PhIP-induced carcinogenesis in mice, and that the carcinogenic activity of PhIP could be affected by the genetic background of the animals. [source] The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studiesCLINICAL ENDOCRINOLOGY, Issue 5 2010Marina Muzza Summary Objective, The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients, The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results, The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l -selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l -selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions, The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer. [source] PRECLINICAL STUDY: Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadolADDICTION BIOLOGY, Issue 1 2010Yuri A. Blednov ABSTRACT ,-Aminobutyric acid (GABA) is synthesized in brain by two isoforms of glutamic acid decarboxylase (Gad), Gad1 and Gad2. Gad1 provides most of the GABA in brain, but Gad2 can be rapidly activated in times of high GABA demand. Mice lacking Gad2 are viable whereas deletion of Gad1 is lethal. We produced null mutant mice for Gad2 on three different genetic backgrounds: predominantly C57BL/6J and one or two generations of backcrossing to 129S1/SvimJ (129N1, 129N2). We used these mice to determine if actions of alcohol are regulated by synthesis of GABA from this isoform. We also studied behavioral responses to a benzodiazepine (flurazepam) and a GABAA receptor agonist (gabaxadol). Deletion of Gad2 increased ethanol palatability and intake and slightly reduced the severity of ethanol-induced withdrawal, but these effects depended strongly on genetic background. Mutant mice on the 129N2 background showed the above three ethanol behavioral phenotypes, but the C57BL/6J inbred background did not show any of these phenotypes. Effects on ethanol consumption also depended on the test as the mutation did not alter consumption in limited access models. Deletion of Gad2 reduced the effect of flurazepam on motor incoordination and increased the effect of extrasynaptic GABAA receptor agonist gabaxadol without changing the duration of loss of righting reflex produced by these drugs. These results are consistent with earlier proposals that deletion of Gad2 (on 129N2 background) reduces synaptic GABA but also suggest changes in extrasynaptic receptor function. [source] Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001R. Gerlai Abstract Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities. [source] Red hair, fair skin and melanoma , melanocortin 1 receptorEXPERIMENTAL DERMATOLOGY, Issue 9 2004J. L. Rees We have previously shown that the MC1R is a key determinant of pigmentary phenotype in man. A range of common and uncommon alleles show diminished function leading to a change in the relative amounts of eumelanin and pheomelanin. As expected, these particular allelic variants are associated with both non-melanoma and melanoma skin cancer and other pigmentary phenotypic characteristics such as freckling. We have recently shown that even against very different genetic backgrounds, the MC1R variants show a phenotypic effect [J Invest Dermatol 2003: 121 (1): 207]. We will present data to explain how the human pigmentary phenotypes can be quantified more appropriately, in terms of both hair melanins and cutaneous response to ultraviolet radiation (submitted and in press). Our results, we would argue, are relevant to those interested in melanocortin signalling in skin and to studies of the genetics of human skin colour and evolution of skin colour. [source] Genetic effects of the soft starch (h) and background loci on volume of starch granules in five inbreds of maizePLANT BREEDING, Issue 2 2000J. A. Wilson Abstract Larger particle volume is beneficial for many aspects of maize starch processing, and may improve the performance of some starch attributes. This study focused on the soft starch (h) locus to identify its potentially influential role in starch particle volume distribution. The objectives were to study the genetic expression of starch particle volume of the h locus in different genetic backgrounds and the gene action conditioning starch particle volume of other loci in both normal-starch and h -starch backgrounds. Forty-five populations (five intra-inbred F1s, 10 hybrid F1s 10 F2s, 10 BC1F1s to h/h parent, and 10 BC1 to h:h conversion of normal parent) were planted in 1993 at two locations and in 1995 at one location. Selfed heterozygotes (±/h) in all generations provided intra-ear comparisons of normal and h starch, and F3 and BC1F2 generations provided inter-ear comparisons. Significant differences were found between normal and h:h genotypes in all intra-ear and inter-ear comparisons. In all cases, general combining ability effects were highly significant, suggesting the presence of additive gene effects. Generation mean analysis of normal and h:h starch materials yielded similar results, indicating the predominance of additive and some dominance effects for other loci on starch particle volume. These results indicate the usefulness of the soft starch gene and additional genetic variation among inbreds in the improvement of starch particle volume for increased starch recovery in wet milling. [source] Lactose Synthase Components in Milk: Concentrations of ,-Lactalbumin and ,1,4-Galactosyltransferase in Milk of Cows from Several Breeds at Various Stages of LactationREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2009GT Bleck Contents It is believed that milk production is determined by the number and activity of mammary secretory cells. Secretory activity, as assessed by milk volume, depends on secretion of the major osmole in milk, lactose, which is produced by lactose synthase. The amount of either of the two proteins in lactose synthase may regulate milk production. The objective of this study was to determine whether the concentrations in milk of the two components of lactose synthase, ,-lactalbumin (,-LA) and ,1,4-galactosyltransferase (B4GALT), were related to genetic background, stage of lactation, breed or parity of dairy cows. ,-Lactalbumin and B4GALT concentrations were measured by ELISA and by enzyme assays, respectively, from single milk samples. Two herds with a total of 279 cows were used in the analysis. One herd contained Ayrshire, Brown Swiss, Holstein and Jersey cows; the second herd contained two groups of cows; Holsteins selected for high milk production and Holsteins with 1960s genetics. The ,-LA concentration in milk was greater in Jerseys and Ayrshires than in Holsteins and Brown Swiss. However, no difference in ,-LA concentration was observed in milk from high and low genetic merit cows in the Minnesota herd or among different genetic backgrounds in the Illinois herd. ,1,4-Galactosyltransferase concentrations were similar for all groups that were analyzed. ,-Lactalbumin concentrations were positively correlated with milk protein concentration, milk fat concentration and lactose concentration. ,1,4-Galactosyltransferase concentration in milk exhibited a strong positive correlation with number of days in milk. Although the concentration of B4GALT increased as lactation progressed, the values did not show any correlation with persistency of lactation or late lactation milk production. In conclusion, this survey shows that the two components of lactose synthase are each correlated to protein concentration and individually correlated to the concentration of other milk components and stage of lactation. [source] Genes located on a SSC17 meat quality QTL region are associated with growth in outbred pig populationsANIMAL GENETICS, Issue 5 2009A. M. Ramos Summary The objective of this study was to evaluate the effect of markers developed in eight genes, located in a previously detected meat quality QTL region on SSC17, on growth, fat and meat quality traits collected in commercial pig populations of different genetic backgrounds. The genes had been previously mapped to SSC17 as part of a fine-mapping effort. Association analyses were conducted between each marker and the available phenotypic traits. Results showed that three genes (CTSZ, CSTF1 and C20orf43) were significantly associated with the growth traits. In addition, CTSZ also impacted on meat colour, with the less favourable genotype for growth being associated with darker meat. The differences observed between genotypes were substantial and may be of economic importance to pig producers. These markers may be useful for selecting for faster growth or improved meat quality. [source] Breaking T cell tolerance against self type II collagen in HLA,DR4,transgenic mice and development of autoimmune arthritisARTHRITIS & RHEUMATISM, Issue 7 2010Tsvetelina Batsalova Objective To establish a new animal model in DRB1*0401 (DR4),transgenic mice in which T cell tolerance to self type II collagen (CII) can be broken and allow for the development of autoimmune arthritis, to investigate the role of posttranslational modifications of the CII259,273 epitope in the induction and breaking of tolerance of DR4-restricted T cells, and to characterize DR4-restricted T cell recognition of the immunodominant CII259,273 epitope. Methods DR4-transgenic mice expressing either the entire human CII protein (HuCII) or only the immunodominant T cell epitope of heterologous CII (MMC) in joint cartilage were established on different genetic backgrounds, and susceptibility to collagen-induced arthritis (CIA) was tested. Results HuCII mice displayed stronger T cell tolerance to heterologous CII than did MMC mice. On the B10 background, arthritis developed only in MMC mice with a defective oxidative burst. However, MMC mice on the C3H background were susceptible to arthritis also with a functional oxidative burst. Significant recall responses in tolerized mice were detected only against the nonglycosylated CII259,273 epitope. Recognition of the CII259,273 epitope was heterogeneous, but the majority of T cells in DR4 mice specifically recognized the nonglycosylated side chain of lysine at position 264. Conclusion It is possible to break tolerance to self CII and induce arthritis in DR4 mice. However, arthritis susceptibility is tightly controlled by the genetic background and by the source of the transgenic element for expressing the heterologous CII peptide as a self CII protein in the joint. In contrast to CIA in Aq -expressing mice, the nonglycosylated CII259,273 epitope is clearly immunodominant in both tolerized and nontolerized DR4 mice. [source] Role of interleukin-17F in chronic inflammatory and allergic lung diseaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006N. Hizawa Summary IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case,control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures. [source] |