Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model
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The KN Motif and AnKyrin Repeat Domain 1 (KANK1) is proposed as a tumour suppressor gene, as its expression is reduced or absent in several types of tumour tissue, and over-expressing the protein inhibited the proliferation of tumour cells in solid cancer models. We report a novel germline loss of heterozygosity mutation encompassing the KANK1 gene in a young patient diagnosed with myelodysplastic neoplasm (MDS) with no additional disease-related genomic aberrations. To study the potential role of KANK1 in haematopoiesis, we generated a new transgenic mouse model with a confirmed loss of KANK1 expression. KANK1 knockout mice did not develop any haematological abnormalities; however, the loss of its expression led to alteration in the colony forming and proliferative potential of bone marrow (BM) cells and a decrease in hematopoietic stem and progenitor cells (HSPCs) population frequency. A comprehensive marker expression analysis of lineage cell populations indicated a role for Kank1 in lymphoid cell development, and total protein analysis suggests the involvement of Kank1 in BM cells’ cytoskeleton formation and mobility.
Originalsprog | Engelsk |
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Artikelnummer | 1947 |
Tidsskrift | Genes |
Vol/bind | 14 |
Udgave nummer | 10 |
ISSN | 2073-4425 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This project was supported by a center grant from the Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem; grant NNF17CC0027852), the Greater Copenhagen Health Science Partners (Clinical Academic Group in Translational Hematology), and Danish Cancer Society (R302-A17259). This project is part of the Danish Research Center for Precision Medicine in Blood Cancers funded by Danish Cancer Society grant R223-A13071.
Publisher Copyright:
© 2023 by the authors.
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