Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model
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Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model. / 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.
I: Genes, Bind 14, Nr. 10, 1947, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model
AU - Almosailleakh, Marwa
AU - Bentivegna, Sofia
AU - Narcisi, Samuele
AU - Benquet, Sébasitien J.
AU - Gillberg, Linn
AU - Montaño-Almendras, Carmen P.
AU - Savickas, Simonas
AU - Schoof, Erwin M.
AU - Wegener, Amelie
AU - Luche, Hérve
AU - Jensen, Henrik E.
AU - Côme, Christophe
AU - Grønbæk, Kirsten
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - germline (GL)
KW - KANK1
KW - lymphoid dysregulation
KW - murine model
KW - myelodysplastic neoplasms (MDS)
U2 - 10.3390/genes14101947
DO - 10.3390/genes14101947
M3 - Journal article
C2 - 37895296
AN - SCOPUS:85175369402
VL - 14
JO - Genes
JF - Genes
SN - 2073-4425
IS - 10
M1 - 1947
ER -
ID: 372825481