Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model

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 h...

Full description

Saved in:

Bibliographic Details
Published in:	Genes Vol. 14; no. 10; p. 1947
Main Authors:	Almosailleakh, Marwa, Bentivegna, Sofia, Narcisi, Samuele, Benquet, Sébasitien J, Gillberg, Linn, Montaño-Almendras, Carmen P, Savickas, Simonas, Schoof, Erwin M, Wegener, Amelie, Luche, Hérve, Jensen, Henrik E, Côme, Christophe, Grønbæk, Kirsten
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 01-10-2023 MDPI
Subjects:	Anemia Animal models Ankyrins Brief Report Cell culture Cell proliferation Cytoskeleton Ethylenediaminetetraacetic acid Flow cytometry Health aspects Hematopoietic stem cells Hemopoiesis Heterozygosity Leukocytes Loss of heterozygosity Mutation Progenitor cells Proteins Software Transgenic mice Tumor suppressor genes Tumors Denmark France Massachusetts United States > US Germany
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2073-4425 2073-4425
DOI:	10.3390/genes14101947