RGD Reference Report - A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia. - Rat Genome Database

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A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia.

Authors: Ordonez-Rueda, D  Jonsson, F  Mancardi, DA  Zhao, W  Malzac, A  Liang, Y  Bertosio, E  Grenot, P  Blanquet, V  Sabrautzki, S  De Angelis, MH  Meresse, S  Duprez, E  Bruhns, P  Malissen, B  Malissen, M 
Citation: Ordonez-Rueda D, etal., Eur J Immunol. 2012 Sep;42(9):2395-408. doi: 10.1002/eji.201242589.
RGD ID: 11040456
Pubmed: PMID:22684987   (View Abstract at PubMed)
DOI: DOI:10.1002/eji.201242589   (Journal Full-text)

Using N-ethyl-N-nitrosourea-induced mutagenesis, we established a mouse model with a novel form of neutropenia resulting from a point mutation in the transcriptional repressor Growth Factor Independence 1 (Gfi1). These mice, called Genista, had normal viability and no weight loss, in contrast to mice expressing null alleles of the Gfi1 gene. Furthermore, the Genista mutation had a very limited impact on lymphopoiesis or on T- and B-cell function. Within the bone marrow (BM), the Genista mutation resulted in a slight increase of monopoiesis and in a block of terminal granulopoiesis. This block occurred just after the metamyelocytic stage and resulted in the generation of small numbers of atypical CD11b(+) Ly-6G(int) neutrophils, the nuclear morphology of which resembled that of mature WT neutrophils. Unexpectedly, once released from the BM, these atypical neutrophils contributed to induce mild forms of autoantibody-induced arthritis and of immune complex-mediated lung alveolitis. They additionally failed to provide resistance to acute bacterial infection. Our study demonstrates that a hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia characterized by a split pattern of functional responses, reflecting the distinct thresholds required for eliciting neutrophil-mediated inflammatory and anti-infectious responses.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GFI1Humanneutropenia  ISOGfi1 (Mus musculus)DNA:mutation:exon:RGD 
Gfi1Ratneutropenia  ISOGfi1 (Mus musculus)DNA:mutation:exon:RGD 
Gfi1Mouseneutropenia  IAGP DNA:mutation:exon:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gfi1  (growth factor independent 1 transcriptional repressor)

Genes (Mus musculus)
Gfi1  (growth factor independent 1 transcription repressor)

Genes (Homo sapiens)
GFI1  (growth factor independent 1 transcriptional repressor)


Additional Information