Dataset Information

The juvenile alopecia mutation (jal) maps to mouse Chromosome 2, and is an allele of GATA binding protein 3 (Gata3).

ABSTRACT: Mice homozygous for the juvenile alopecia mutation (jal) display patches of hair loss that appear as soon as hair develops in the neonatal period and persist throughout life. Although a report initially describing this mouse variant suggested that jal maps to mouse Chromosome 13, our preliminary mapping analysis did not support that claim.To map jal to a particular mouse chromosome, we produced a 103-member intraspecific backcross panel that segregated for jal, and typed it for 93 PCR-scorable, microsatellite markers that are located throughout the mouse genome. Only markers from the centromeric tip of Chromosome 2 failed to segregate independently from jal, suggesting that jal resides in that region. To more precisely define jal's location, we characterized a second, 374-member backcross panel for the inheritance of five microsatellite markers from proximal Chromosome 2. This analysis restricted jal's position between D2Mit359 and D2Mit80, an interval that includes Il2ra (for interleukin 2 receptor, alpha chain), a gene that is known to be associated with alopecia areata in humans. Complementation testing with an engineered null allele of Il2ra, however, showed that jal is a mutation in a distinct gene. To further refine the location of jal, the 374-member panel was typed for a set of four single-nucleotide markers located between D2Mit359 and D2Mit80, identifying a 0.55?Mb interval where jal must lie. This span includes ten genes-only one of which, Gata3 (for GATA binding protein 3)-is known to be expressed in skin. Complementation testing between jal and a Gata3 null allele produced doubly heterozygous, phenotypically mutant offspring.The results presented indicate that the jal mutation is a mutant allele of the Gata3 gene on mouse Chromosome 2. We therefore recommend that the jal designation be changed to Gata3jal, and suggest that this mouse variant may provide an animal model for at least some forms of focal alopecia that have their primary defect in the hair follicle and lack an inflammatory component.

SUBMITTER: Ramirez F

PROVIDER: S-EPMC3656803 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The juvenile alopecia mutation (jal) maps to mouse Chromosome 2, and is an allele of GATA binding protein 3 (Gata3).

Ramirez Francisco F Feliciano Aaron M AM Adkins Elisabeth B EB Child Kevin M KM Radden Legairre A LA Salas Alexis A Vila-Santana Nelson N Horák José M JM Hughes Samantha R SR Spacek Damek V DV King Thomas R TR

BMC genetics 20130509

<h4>Background</h4>Mice homozygous for the juvenile alopecia mutation (jal) display patches of hair loss that appear as soon as hair develops in the neonatal period and persist throughout life. Although a report initially describing this mouse variant suggested that jal maps to mouse Chromosome 13, our preliminary mapping analysis did not support that claim.<h4>Results</h4>To map jal to a particular mouse chromosome, we produced a 103-member intraspecific backcross panel that segregated for jal, ...[more]

PMID: 23659281

Similar Datasets

Project description:BackgroundGATA3 is a transcription factor that is important during development and plays a role in differentiation and activity of immune cells, particularly T cells. Abnormal T cell function is found in autoimmune arthritis. We present the first known case of autoimmune arthritis associated with a novel GATA3 mutation.MethodsWhole exome sequencing of the proband was performed on a clinical basis. Peripheral blood mononuclear cells (PBMCs) were collected from the proband, healthy sibling, and parent. cDNA prepared from RNA was analyzed with polymerase chain reaction and Sanger sequencing. Intracellular proteins were assessed by immunoblot of PBMC homogenates. GATA3 in vitro activity was measured in HeLa cell cultures expressing a mammalian expression vector containing GATA3 or mutants generated by site-directed mutagenesis. GATA3 transcriptional activity was examined using a luciferase reporter assay system. T helper cell ex vivo function was evaluated by stimulating PBMCs to differentiate into effector T cells along Th0, Th1, Th2, and Th17 lineages, and re-stimulating effector cells to secrete cytokines. Cytokine production was measured by enzyme-linked immunosorbent assay.ResultsThe proband is the first known case of autoimmune arthritis associated with a mutation in GATA3. The proband M401VfsX106 protein is expressed and has a dominant negative function on GATA3 transcriptional activity. The proband PBMCs have markedly increased differentiation along the Th1 and Th17 pathways, with decreased differentiation along the Th2 pathway. Unexpectedly, Th0 cells from the proband express high levels of IFNγ.ConclusionsOur research presents the first known case of autoimmune arthritis associated with a mutation in GATA3. This work expands the phenotypic spectrum of GATA3 mutations. It reveals the novel insight that decreased and altered GATA3 activity coincides with autoimmune arthritis. This work suggests that modulation of GATA3 may be a therapeutic approach for patients with autoimmune arthritis.

Dataset Information

The juvenile alopecia mutation (jal) maps to mouse Chromosome 2, and is an allele of GATA binding protein 3 (Gata3).

Publications

The juvenile alopecia mutation (jal) maps to mouse Chromosome 2, and is an allele of GATA binding protein 3 (Gata3).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets