Primary antibody deficiencies.

Primary antibody deficiencies are characterized by the inability to effectively produce antibodies and may involve defects in B-cell development or maturation. Primary antibody deficiencies can occur at any age, depending on the disease pathology. Certain primary antibody deficiencies affect males and females equally, whereas others affect males more often.

Depletion of results in age-dependent changes in DNA methylation and gene expression in a zebrafish model of myelodysplastic syndrome.

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (2), a dioxygenase enzyme that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, is a recurrently mutated tumor suppressor gene in MDS and other myeloid malignancies. Previously, we reported a stable zebrafish line with a loss-of-function mutation in the gene.

Disruption of results in myeloproliferative neoplasms in zebrafish.

Somatic loss-of-function mutations of the additional sex combs-like transcriptional regulator 1 () gene are common genetic abnormalities in human myeloid malignancies and induce clonal expansion of mutated hematopoietic stem cells (HSCs). To understand how disruption leads to myeloid cell transformation, we generated haploinsufficient and null zebrafish lines using genome-editing technology. Here, we show that homozygous loss of leads to apoptosis of newly formed HSCs.

A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing.

The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations of TET2 are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain.