Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice

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Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice. / Christensen, Jane H; Nielsen, Marit N; Hansen, Jakob; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; West, Mark; Corydon, Thomas J; Gregersen, Niels; Bross, Peter.

In: Cell Stress & Chaperones, Vol. 15, No. 6, 2010, p. 851-863.

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@article{5ef6c37058fb11df9806000ea68e967b,
title = "Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice",
abstract = "The mitochondrial Hsp60 chaperonin plays an important role in sustaining cellular viability. Its dysfunction is related to inherited forms of the human diseases spastic paraplegia and hypomyelinating leukodystrophy. However, it is unknown whether the requirement for Hsp60 is neuron specific or whether a complete loss of the protein will impair mammalian development and postnatal survival. In this study, we describe the generation and characterization of a mutant mouse line bearing an inactivating gene-trap insertion in the Hspd1 gene encoding Hsp60. We found that heterozygous mice were born at the expected ratio compared to wild-type mice and displayed no obvious phenotype deficits. Using quantitative reverse transcription PCR, we found significantly decreased levels of the Hspd1 transcript in all of the tissues examined, demonstrating that the inactivation of the Hspd1 gene is efficient. By Western blot analysis, we found that the amount of Hsp60 protein, compared to either cytosolic tubulin or mitochondrial voltage-dependent anion-selective channel protein 1/porin, was decreased as well. The expression of the nearby Hspe1 gene, which encodes the Hsp10 co-chaperonin, was concomitantly down regulated in the liver, and the protein levels in all tissues except the brain were reduced. Homozygous Hspd1 mutant embryos, however, died shortly after implantation (day 6.5 to 7.5 of gestation, Theiler stages 9-10). Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice, while reducing the amount of Hsp60 by inactivation of one allele of the gene is compatible with survival to term as well as postnatal life.",
author = "Christensen, {Jane H} and Nielsen, {Marit N} and Jakob Hansen and Annette F{\"u}chtbauer and Ernst-Martin F{\"u}chtbauer and Mark West and Corydon, {Thomas J} and Niels Gregersen and Peter Bross",
year = "2010",
doi = "10.1007/s12192-010-0194-x",
language = "English",
volume = "15",
pages = "851--863",
journal = "Cell Stress & Chaperones",
issn = "1355-8145",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice

AU - Christensen, Jane H

AU - Nielsen, Marit N

AU - Hansen, Jakob

AU - Füchtbauer, Annette

AU - Füchtbauer, Ernst-Martin

AU - West, Mark

AU - Corydon, Thomas J

AU - Gregersen, Niels

AU - Bross, Peter

PY - 2010

Y1 - 2010

N2 - The mitochondrial Hsp60 chaperonin plays an important role in sustaining cellular viability. Its dysfunction is related to inherited forms of the human diseases spastic paraplegia and hypomyelinating leukodystrophy. However, it is unknown whether the requirement for Hsp60 is neuron specific or whether a complete loss of the protein will impair mammalian development and postnatal survival. In this study, we describe the generation and characterization of a mutant mouse line bearing an inactivating gene-trap insertion in the Hspd1 gene encoding Hsp60. We found that heterozygous mice were born at the expected ratio compared to wild-type mice and displayed no obvious phenotype deficits. Using quantitative reverse transcription PCR, we found significantly decreased levels of the Hspd1 transcript in all of the tissues examined, demonstrating that the inactivation of the Hspd1 gene is efficient. By Western blot analysis, we found that the amount of Hsp60 protein, compared to either cytosolic tubulin or mitochondrial voltage-dependent anion-selective channel protein 1/porin, was decreased as well. The expression of the nearby Hspe1 gene, which encodes the Hsp10 co-chaperonin, was concomitantly down regulated in the liver, and the protein levels in all tissues except the brain were reduced. Homozygous Hspd1 mutant embryos, however, died shortly after implantation (day 6.5 to 7.5 of gestation, Theiler stages 9-10). Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice, while reducing the amount of Hsp60 by inactivation of one allele of the gene is compatible with survival to term as well as postnatal life.

AB - The mitochondrial Hsp60 chaperonin plays an important role in sustaining cellular viability. Its dysfunction is related to inherited forms of the human diseases spastic paraplegia and hypomyelinating leukodystrophy. However, it is unknown whether the requirement for Hsp60 is neuron specific or whether a complete loss of the protein will impair mammalian development and postnatal survival. In this study, we describe the generation and characterization of a mutant mouse line bearing an inactivating gene-trap insertion in the Hspd1 gene encoding Hsp60. We found that heterozygous mice were born at the expected ratio compared to wild-type mice and displayed no obvious phenotype deficits. Using quantitative reverse transcription PCR, we found significantly decreased levels of the Hspd1 transcript in all of the tissues examined, demonstrating that the inactivation of the Hspd1 gene is efficient. By Western blot analysis, we found that the amount of Hsp60 protein, compared to either cytosolic tubulin or mitochondrial voltage-dependent anion-selective channel protein 1/porin, was decreased as well. The expression of the nearby Hspe1 gene, which encodes the Hsp10 co-chaperonin, was concomitantly down regulated in the liver, and the protein levels in all tissues except the brain were reduced. Homozygous Hspd1 mutant embryos, however, died shortly after implantation (day 6.5 to 7.5 of gestation, Theiler stages 9-10). Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice, while reducing the amount of Hsp60 by inactivation of one allele of the gene is compatible with survival to term as well as postnatal life.

U2 - 10.1007/s12192-010-0194-x

DO - 10.1007/s12192-010-0194-x

M3 - Journal article

C2 - 20393889

VL - 15

SP - 851

EP - 863

JO - Cell Stress & Chaperones

JF - Cell Stress & Chaperones

SN - 1355-8145

IS - 6

ER -