BP1 is a negative modulator of definitive erythropoiesis.
Beta protein 1 (BP1), a human homeotic transcription factor, is expressed during hematopoeisis in the erythroid lineage. To determine the in vivo role of BP1 in erythropoiesis, we have undertaken two complementary approaches using enforced BP1 expression in both transgenic mice and embryonic stem (ES) cells. Despite repeated attempts, only one adult transgenic BP1 founder mouse among 121 mice was obtained. This mouse presumably survived due to transgene mosaicism because the transgene could not be transmitted. This mouse expressed BP1 and displayed splenomegaly, extramedullary erythropoiesis and severe amyloidosis A in the kidney, a phenotype compatible with thalassemia. Consistently, the presence of BP1 transgene in fetuses was associated with paleness and lethality. In ES cells, BP1 expression in primary differentiation appeared to antagonize adult beta-globin expression. In secondary differentiation, BP1 expression reduced significantly beta-globin gene expression in both primitive and definitive erythroid cells, whereas it impaired only the definitive erythroid cell differentiation. These studies showed that BP1 can negatively modulate adult beta-globin gene expression and definitive erythroid cell differentiation, and suggest that BP1 could play a role in thalassemia.
Mpollo
Marthe-Sandrine Eiymo Mwa
MS
Molecular Genetics and Development, Institut de Recherches Cliniques de Montreal, Faculte de Medecine de l'Universite de Montreal, 110 ouest avenue des Pins, Montreal, Quebec, Canada H2W 1R7.
Beaudoin
Mélissa
M
Berg
Patricia E
PE
Beauchemin
Hugues
H
D'Agati
Vivette
V
Trudel
Marie
M
D000686:Amyloidosis / Q000473:pathology; D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis; D005804:Genes, Lethal; D005914:Globins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D005914:Globins