Document Type
Article
Publication Date
7-2-2025
Original Citation
Nesbit C,
Martin W,
Czechanski A,
Byers C,
Raghupathy N,
Ferraj A,
Stumpff J,
Reinholdt L.
Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression. Sci Rep. 2025;15(1):23046.
Keywords
JMG, SS1, Kinesins, Animals, Mitosis, Mice, Fertility, Male, Female, Humans
JAX Source
Sci Rep. 2025;15(1):23046.
ISSN
2045-2322
PMID
40596695
DOI
https://doi.org/10.1038/s41598-025-08766-w
Grant
he Scientific Services at the Jackson Laboratory are par- tially supported by the National Cancer Institute under award number P30CA034196. Additionally, the research reported in this publication was supported by a grant from the National Institutes of Childhood Health and Dis- ease (R03HD078485 to L.G.R), a pilot award from the Cancer Center at The Jackson Laboratory (P30CA034196 to L.G.R. and J.S.), and an Outstanding Investigator Award (R35GM144133 to J.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Abstract
The kinesin family member 18 A (KIF18A) is an essential regulator of microtubule dynamics and chromosome alignment during mitosis. Functional dependency on KIF18A varies by cell type and genetic context but the heritable factors that influence this dependency remain unknown. To address this, we took advantage of the variable penetrance observed in different mouse strain backgrounds to screen for loci that modulate germ cell depletion in the absence of KIF18A. We found a significant association at a Chr5 locus where anaphase promoting complex subunits 5 (Anapc5) and 7 (Anapc7) were the top candidate genes. We found that both genes were differentially expressed in a sensitive strain background when compared to resistant strain background at key timepoints in gonadal development. We also identified a novel retroviral insertion in Anapc7 that may in part explain the observed expression differences. In cell line models, we found that depletion of KIF18A induced mitotic arrest, which was partially rescued by co-depletion of ANAPC7 (APC7) and exacerbated by co-depletion of ANAPC5 (APC5). These findings suggest that differential expression and activity of Anapc5 and Anapc7 may influence sensitivity to KIF18A depletion in germ cells and CIN cells, with potential implications for optimizing antineoplastic therapies.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.