title: Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds.
abstract: All mice harboring the X-linked Gata1low mutation in a predominantly CD1 background are born anemic and thrombocytopenic. They recover from anemia at 1 month of age but remain thrombocytopenic all their life and develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, at 12 months. The effects of the genetic background on the myelofibrosis developed by Gata1low mice was assessed by introducing the mutation, by standard genetic approaches, in the C57BL/6 and DBA/2 backgrounds and by analyzing the phenotype of the different mutants at 12 to 13 (by histology) and 16 to 20 (by cytofluorimetry) months of age. Although all the Gata1low mice developed fibrosis at 12 to 13 months, variegations were observed in the severity of the phenotype expressed by mutants of different backgrounds. In C57BL/6 mice, the mutation was no longer inherited in a Mendelian fashion, and fibrosis was associated with massive osteosclerosis. Instead, DBA/2 mutants, although severely anemic, expressed limited fibrosis and osteosclerosis and did not present tear-drop poikilocytes in blood or extramedullary hemopoiesis in liver up to 20 months of age. We propose that the variegation in myelofibrosis expressed by Gata1low mutants of different strains might represent a model to study the variability of the clinical picture of the human disease.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Martelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ghinassi
authors.forename: Barbara
authors.initials: B
authors.lastname: Panetta
authors.forename: Elena
authors.initials: E
authors.lastname: Alfani
authors.forename: Valentina
authors.initials: V
authors.lastname: Gatta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pancrazzi
authors.forename: Costanza
authors.initials: C
authors.lastname: Bogani
authors.forename: Alessandro Maria
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Paoletti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Migliaccio
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D015415:Biomarkers; D001789:Blood Group Antigens / Q000378:metabolism; D004900:Erythroblasts / Q000378:metabolism; D005269:Femur / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D006410:Hematopoiesis; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010026:Osteosclerosis / Q000378:metabolism; D010641:Phenotype; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: C000593749:ATXN1 protein, human; D015703:Antigens, CD; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D015415:Biomarkers; D001789:Blood Group Antigens; D050982:GATA1 Transcription Factor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C489122:TER-119 antigen, mouse; D016212:Transforming Growth Factor beta