Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions.
Cyclical neutropenia is usually caused by heterozygous <i>ELANE</i> mutations while congenital neutropenia is genetically heterogeneous with mutations in genes like <i>ELANE, HAX-1, G6PC3</i> and <i>GFI1.</i> The presence of <i>ELANE</i> mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia such as autoimmune cytopenia and evolving aplasia.
In the mouse, Gfi1 deficiency causes neutropenia and an accumulation of granulomonocytic precursor cells that is reminiscent of a myelodysplastic syndrome.
In an effort to identify Gfi1-interacting proteins and also to generate new candidate genes causing neutropenia, we performed a yeast two-hybrid screen with Gfi1.
We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref.3).