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

• 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
• DOI: 10.3390/genes14101947
• EISSN: 2073-4425

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.