Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice

Badalová, Jana; Svobodová, Milena; Havelková, Helena; Vladimirov, Vladimir I.; Vojtíšková, Jarmila; Engová, J; Pilčı́k, Tomáš; Volf, Petr; Démant, Peter; Lipoldová, Marie

doi:10.1038/sj.gene.6363838

Cited by 26 publications

(44 citation statements)

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“…Also, the CcS/ Dem strains, which were also used in our experiments, have already been successfully used by different groups. Lipoldova et al for example were able to identify five novel L. major resistance loci using CcS05 17 and Havelkova et al 46 used CcS09 and CcS11 for the identification of genes involved in T-cell-receptor-induced activation.…”

Section: Discussionmentioning

confidence: 99%

“…Given the considerable homology between the human and mouse genome, the mouse has proven to be a useful genetic model for complex human diseases. 17,18 Furthermore, genetic homogeneity and strictly controlled environmental conditions are major advantages of mouse models as well as the fact that the mouse 'toolbox' (gene-targeted mice, genetic and physical map) is very well developed.…”

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

“…33 The BALB/c mice produce high serum IgE levels whereas the STS/A shows low serum IgE levels after Leishmania major infection. 17 This series of RC strains has been used to dissect the genetics of T-cell activation and several models of inflammatory diseases, including Mycobacterium tuberculosis and L. major infection. 17,[19][20][21][22][23][24][25]27 In the present study, we used the CcS/Dem series to determine the susceptibility of each strain and both parental strains BALB/cHeA and STS/A for antigeninduced airway manifestations of asthma as described by Deurloo et al 34 Generated data were used to calculate correlations between the different asthma-related characteristics for all individual strains and in the pooled population.…”

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

“…18 In several diseases, the recombinant congenic (RC) strains of mice have proven to be a powerful tool to provide the mapping of genes controlling complex traits. 17,[19][20][21][22][23][24][25][26][27] A series of RC strains comprises approximately 20 homozygous strains, each of which contains on average 87.5% genes of a common background strain and 12.5% of a common donor strain. 26,28 In this way, the RC system transforms a multigenic difference into a set of mono-or oligogenic differences and hence offers higher resolution power in mapping the quantitative trait loci and detecting their mutual interactions than the standard genetic methods.…”

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

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Mouse genetic model for antigen-induced airway manifestations of asthma

et al. 2006

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Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic (RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a 'modified' Th2 response except CcS14, which shows a 'true' Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped.

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Section: Discussionmentioning

confidence: 99%

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

Section: Polymorphisms Of Both Adam33 and Spink5mentioning

confidence: 99%

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Mouse genetic model for antigen-induced airway manifestations of asthma

et al. 2006

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“…25 Other studies examined mouse crosses for host genes controlling response to infection. These included evidence for and mapping of multiple genes controlling IgE levels in Leishmania major infected mice 26 as well as a study implicating SLC11A1 (NRAMP1) in the persistence of Salmonella infection in mice. 27 Another provocative study linked a gp130 gene 'knock-in' with susceptibility to Listeria infection.…”

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confidence: 99%

Looking back and looking forward

Seldin¹,

Gallagher

2003

Genes Immun

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Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12

et al. 2008

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Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors. In spite of progress in the study of heredity of atopy, the genetic mechanisms of IgE regulation have not yet been completely elucidated. The analysis of complex traits can benefit considerably from integration of human and mouse genetics. Previously, we mapped a mouse IgE-controlling locus Lmr9 on chromosome 4 to a segment of <9 Mb. In this study, we tested levels of total IgE and 25 specific IgEs against inhalant and food allergens in 67 Czech atopic families. In the position homologous to Lmr9 on chromosome 8q12 marked by D8S285, we demonstrated a novel human IgE-controlling locus exhibiting suggestive linkage to composite inhalant allergic sensitization (limit of detection, LOD = 2.11, P = 0.0009) and to nine specific IgEs, with maximum LOD (LOD = 2.42, P = 0.0004) to plantain. We also tested 16 markers at previously reported chromosomal regions of atopy. Linkage to plant allergens exceeding the LOD > 2.0 was detected at 5q33 (D5S1507, LOD = 2.11, P = 0.0009) and 13q14 (D13S165, LOD = 2.74, P = 0.0002). The significant association with plant allergens (quantitative and discrete traits) was found at 7p14 (D7S2250, corrected P = 0.026) and 12q13 (D12S1298, corrected P = 0.043). Thus, the finding of linkage on chromosome 8q12 shows precision and predictive power of mouse models in the investigation of complex traits in humans. Our results also confirm the role of loci at 5q33, 7p14, 12q14, and 13q13 in control of IgE.

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Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice

Abstract: The strain BALB/cHeA (BALB/c) is a high producer, and STS/A (STS) a low producer of IgE after Leishmania major infection. We analyzed this strain difference using 20 recombinant congenic (RC) BALB/c-c-STS/Dem (CcS

Cited by 26 publications

References 32 publications

Mouse genetic model for antigen-induced airway manifestations of asthma

Mouse genetic model for antigen-induced airway manifestations of asthma

Looking back and looking forward

Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12

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