To map a potential locus corresponding to the CD23low phenotype

ABSTRACT: CD23, the low affinity receptor for IgE, has been proposed to play a critical role in the regulation of IgE production, based on altered IgE levels in CD23-deficient mice and transgenic mouse models, as well as in mouse strains with mutations in the CD23 gene, e.g. 129 substrains. Here, we have investigated a mouse line termed LxT1 that expresses reduced CD23 surface levels on B cells, and its influence on IgE production. Extensive phenotypic analyses showed that CD23 surface expression was reduced in LxT1 compared to the control, without affecting B cell development in general. We linked the CD23low surface level in LxT1 mice to a recessive locus, a 129-derived region spanning 28Mb on chromosome 8, which includes the CD23 gene. Sequence analysis confirmed the five mutations within the CD23 coding region in LxT1 mice, the same as those present in NZB and 129 substrains. However, this CD23low phenotype was not observed in all 129 substrains despite carrying these same CD23 mutations in the coding region. Affymetrix Mouse Diversity Genotyping Array was performed according to the manufacturer's directions on DNA extracted from crossed mice samples. The array can interrogate more than 623,000SNPs, yielding an average SNP density of one marker per 4.3kb. Genetic linkage analysis was performed to exploit the co-segregation of chromosomal regions with the CD23 phenotype to identify the location of causative genes. To map a potential mutation, male LxT1 mice were crossed to female BALB/c mice to generate F1 mice. Two females from the F1 litters were backcrossed to the parental male LxT1 to generate N2 mice for analysis of phenotype and genetic mapping. N2 mice with (n=6) and without (n=5) CD23low surface level and (n=1) BALB/c were used to map putative genetic alteration that may cause the CD23low phenotype.

ORGANISM(S): Mus musculus

SUBMITTER: Weicheng Ren 

PROVIDER: E-GEOD-44231 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress