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Dev Biol. 2015 Jun 15;402(2):253-262. doi: 10.1016/j.ydbio.2015.03.011. Epub 2015 Mar 28.

Kif18a is specifically required for mitotic progression during germ line development.

Author information

1
The Jackson Laboratory, Genetic Resource Science, Bar Harbor, ME 04609.
2
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405.
#
Contributed equally

Abstract

Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in the germ line to ensure genome integrity. We previously showed that the primary phenotype of germ cell deficient 2 (gcd2) mutant mice is infertility due to germ cell depletion during embryogenesis. Here we show that the underlying mutation is a mis-sense mutation, R308K, in the motor domain of the kinesin-8 family member, KIF18A, a protein that is expressed in a variety of proliferative tissues and is a key regulator of chromosome alignment during mitosis. Despite the conservative nature of the mutation, we show that its functional consequences are equivalent to KIF18A deficiency in HeLa cells. We also show that somatic cells progress through mitosis, despite having chromosome alignment defects, while germ cells with similar chromosome alignment defects undergo mitotic arrest and apoptosis. Our data provide evidence for differential requirements for chromosome alignment in germ and somatic cells and show that Kif18a is one of a growing number of genes that are specifically required for cell cycle progression in proliferating germ cells.

KEYWORDS:

Cell cycle; Gametogenesis; Germ cells; Kinesin; Laboratory mouse; Mitosis; Mitotic spindle

PMID:
25824710
PMCID:
PMC4450139
DOI:
10.1016/j.ydbio.2015.03.011
[Indexed for MEDLINE]
Free PMC Article
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