Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-46880
Gravemann, S; Schnipper, N; Meyer, H; Vaya, A; Nowaczyk, M J; Rajab, A; Hofmann, W K; Salewsky, B; Tönnies, H; Neitzel, H; Stassen, H H; Sperling, K; Hoffmann, K (2010). Dosage effect of zero to three functional LBR-genes in vivo and in vitro. Nucleus, 1(2):179-189.
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The Lamin B receptor (LBR) is a pivotal architectural protein in the nuclear envelope. Mutations in the Lamin B receptor lead to nuclear hyposegmentation (Pelger-Huët anomaly). We have exactly quantified the nuclear lobulation in neutrophils from individuals with 0, 1, 2 and 3 functional copies of the lamin B receptor gene and analyzed the effect of different mutation types. Our data demonstrate that there is a highly significant gene-dosage effect between the gene copy number and the nuclear segmentation index of neutrophils. This finding is paralleled by a dose-dependent increase in LBR protein and staining intensity of the nuclear membrane in corresponding lymphoblastoid cell lines, which demonstrates a significant correlation on the protein level as well. We further show that LBR expression continually increases during granulopoiesis in vitro from human precursor cells with ovoid nuclei to multi-segmented neutrophil nuclei 11 days later, indicating relevance for regular human granulopoiesis. Altogether, LBR is a unique model that will allow the systematic study of gene-dosage effects and of modifying endogeneous and exogeneous factors on granulopoiesis.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Response Genetics|
|Deposited On:||27 Feb 2011 14:41|
|Last Modified:||28 Oct 2013 20:08|
|Free access at:||PubMed ID. An embargo period may apply.|
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