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SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities

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SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities. / Ju, Limei; Wing, Jonathon; Taylor, Elaine; Brandt, Renata; Slijepcevic, Predrag; Horsch, Marion; Rathkolb, Birgit; Racz, Ildiko; Becker, Lore; Hans, Wolfgang; Adler, Thure; Beckers, Johannes; Rozman, Jan; Klingenspor, Martin; Wolf, Eckhard; Zimmer, Andreas; Klopstock, Thomas; Busch, Dirk; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabe de Angelis, Martin; van der Horst, Gilbertus; Lehmann, Alan.

In: DNA Repair, Vol. 12, No. 5, 01.05.2013, p. 356-366.

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Ju, L, Wing, J, Taylor, E, Brandt, R, Slijepcevic, P, Horsch, M, Rathkolb, B, Racz, I, Becker, L, Hans, W, Adler, T, Beckers, J, Rozman, J, Klingenspor, M, Wolf, E, Zimmer, A, Klopstock, T, Busch, D, Gailus-Durner, V, Fuchs, H, Hrabe de Angelis, M, van der Horst, G & Lehmann, A 2013, 'SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities' DNA Repair, vol. 12, no. 5, pp. 356-366. https://doi.org/10.1016/j.dnarep.2013.02.006

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Ju, Limei ; Wing, Jonathon ; Taylor, Elaine ; Brandt, Renata ; Slijepcevic, Predrag ; Horsch, Marion ; Rathkolb, Birgit ; Racz, Ildiko ; Becker, Lore ; Hans, Wolfgang ; Adler, Thure ; Beckers, Johannes ; Rozman, Jan ; Klingenspor, Martin ; Wolf, Eckhard ; Zimmer, Andreas ; Klopstock, Thomas ; Busch, Dirk ; Gailus-Durner, Valerie ; Fuchs, Helmut ; Hrabe de Angelis, Martin ; van der Horst, Gilbertus ; Lehmann, Alan. / SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities. In: DNA Repair. 2013 ; Vol. 12, No. 5. pp. 356-366.

Bibtex

@article{6e91269074184ceea46fae0b85bca927,
title = "SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities",
abstract = "Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes. In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination. siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents. In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene. A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals. However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype. With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans. When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns. Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C. They also accumulated more oxidative damage than wild-type cells.",
keywords = "DNA repair, Mouse model",
author = "Limei Ju and Jonathon Wing and Elaine Taylor and Renata Brandt and Predrag Slijepcevic and Marion Horsch and Birgit Rathkolb and Ildiko Racz and Lore Becker and Wolfgang Hans and Thure Adler and Johannes Beckers and Jan Rozman and Martin Klingenspor and Eckhard Wolf and Andreas Zimmer and Thomas Klopstock and Dirk Busch and Valerie Gailus-Durner and Helmut Fuchs and {Hrabe de Angelis}, Martin and {van der Horst}, Gilbertus and Alan Lehmann",
year = "2013",
month = "5",
day = "1",
doi = "10.1016/j.dnarep.2013.02.006",
language = "English",
volume = "12",
pages = "356--366",
journal = "DNA Repair",
issn = "1568-7864",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities

AU - Ju, Limei

AU - Wing, Jonathon

AU - Taylor, Elaine

AU - Brandt, Renata

AU - Slijepcevic, Predrag

AU - Horsch, Marion

AU - Rathkolb, Birgit

AU - Racz, Ildiko

AU - Becker, Lore

AU - Hans, Wolfgang

AU - Adler, Thure

AU - Beckers, Johannes

AU - Rozman, Jan

AU - Klingenspor, Martin

AU - Wolf, Eckhard

AU - Zimmer, Andreas

AU - Klopstock, Thomas

AU - Busch, Dirk

AU - Gailus-Durner, Valerie

AU - Fuchs, Helmut

AU - Hrabe de Angelis, Martin

AU - van der Horst, Gilbertus

AU - Lehmann, Alan

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes. In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination. siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents. In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene. A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals. However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype. With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans. When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns. Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C. They also accumulated more oxidative damage than wild-type cells.

AB - Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes. In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination. siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents. In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene. A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals. However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype. With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans. When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns. Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C. They also accumulated more oxidative damage than wild-type cells.

KW - DNA repair

KW - Mouse model

U2 - 10.1016/j.dnarep.2013.02.006

DO - 10.1016/j.dnarep.2013.02.006

M3 - Journal article

VL - 12

SP - 356

EP - 366

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

IS - 5

ER -