CELL THERAPY AND COMPOSITIONS THEREFOR

摘要

The zebrafish marsanne mutant comprises a loss of function mutation in the ZBTB11 gene and provides a teleost model of ZBTB11 deficiency-associated neutrophil mediated tissue injury, neutropenia, inflammation, hyperplasia, immunodeficiency, central nervous system degeneration, hydrocephalus, are of haematological malignancies and myelopoietic disorders such as lymphoma and myeloid leukemia. Agents that down regulate ZBTB11 gene expression in zebrafish also induced neutropenia and hydrocephalus which are characteristics of the marsanne mutant phenotype. Conversely, replacement of human or zebrafish protein corrected the phenotype in zebrafish. A method for identifying or assessing a variant or analog of ZBTB11 nucleic acid or protein or an agent which modulates a condition associated with ZBTB11 dysregulation (deficiency) in a subject is provided, the method comprising (i) contacting the agent or variant or analog with a teleost model of ZBTB11 deficiency; and (ii) assessing the ability of the agent or variant or analog to rescue (complement) the phenotype of the teleost model. A method of treating or preventing a condition associated with ZBTB11 dysregulation in a subject is provided, the method comprising administering a composition that comprises an agent that modulates the level or activity of ZBTB11 polypeptide or a complex comprising same or the level or activity of ZBTB11 polynucleotide in the subject. Zebrafish ZBTB11 polynucleotides and polypeptides and parts and variants thereof are provided together with antibodies or antibody fragments determined thereby and cellular agents, teleost models or vectors comprising same.