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PMID:7926765
| Citation |
van der Lugt, NM, Domen, J, Linders, K, van Roon, M, Robanus-Maandag, E, te Riele, H, van der Valk, M, Deschamps, J, Sofroniew, M and van Lohuizen, M (1994) Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 8:757-69 |
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| Abstract |
The bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the Drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells. Null mutant mice display three phenotypic alterations: (1) a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens; (2) neurological abnormalities manifested by an ataxic gait and sporadic seizures; and (3) posterior transformation, in most cases along the complete anteroposterior axis of the skeleton. The observations indicate that Mbi-1 plays an important role in morphogenesis during embryonic development and in hematopoiesis throughout pre- and postnatal life. Furthermore, these data provide the first evidence of functional conservation of a mammalian Polycomb group homolog. |
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| Keywords |
Animals; Ataxia/genetics; Bone Marrow Cells; Brain/abnormalities; Embryonic and Fetal Development; Female; Gene Expression Regulation, Developmental; Gene Targeting; Germ-Line Mutation/physiology; Hematopoietic System/abnormalities; Hematopoietic System/cytology; Lymphocyte Activation; Male; Mice; Mice, Transgenic; Mitogens/pharmacology; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogenes; Recombination, Genetic; Repressor Proteins; Ribs/abnormalities; Seizures/genetics; Spine/abnormalities; Spleen/cytology; Thymus Gland/cytology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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