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An animal model for Pierpont syndrome : a mouse bearing the Tbl1xr1Y446C/Y446C mutation. / Hu, Yalan; Lauffer, Peter; Stewart, Michelle et al.

In: Human molecular genetics, Vol. 31, No. 17, 25.08.2022, p. 2951-2963.

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Hu Y, Lauffer P, Stewart M, Codner G, Mayerl S, Heuer H et al. An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation. Human molecular genetics. 2022 Aug 25;31(17):2951-2963. https://doi.org/10.1093/hmg/ddac086

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Hu, Yalan ; Lauffer, Peter ; Stewart, Michelle et al. / An animal model for Pierpont syndrome : a mouse bearing the Tbl1xr1Y446C/Y446C mutation. In: Human molecular genetics. 2022 ; Vol. 31, No. 17. pp. 2951-2963.

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@article{7328dc3453494258b4f46b4b79053a18,
title = "An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation",
abstract = "Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.",
author = "Yalan Hu and Peter Lauffer and Michelle Stewart and Gemma Codner and Steffen Mayerl and Heike Heuer and Lily Ng and Douglas Forrest and {van Trotsenburg}, Paul and Aldo Jongejan and Eric Fliers and Raoul Hennekam and Anita Boelen",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2022",
month = aug,
day = "25",
doi = "10.1093/hmg/ddac086",
language = "English",
volume = "31",
pages = "2951--2963",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "17",

}

RIS

TY - JOUR

T1 - An animal model for Pierpont syndrome

T2 - a mouse bearing the Tbl1xr1Y446C/Y446C mutation

AU - Hu, Yalan

AU - Lauffer, Peter

AU - Stewart, Michelle

AU - Codner, Gemma

AU - Mayerl, Steffen

AU - Heuer, Heike

AU - Ng, Lily

AU - Forrest, Douglas

AU - van Trotsenburg, Paul

AU - Jongejan, Aldo

AU - Fliers, Eric

AU - Hennekam, Raoul

AU - Boelen, Anita

N1 - Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2022/8/25

Y1 - 2022/8/25

N2 - Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.

AB - Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.

UR - http://www.scopus.com/inward/record.url?scp=85137138498&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddac086

DO - 10.1093/hmg/ddac086

M3 - Article

C2 - 35416977

VL - 31

SP - 2951

EP - 2963

JO - Human molecular genetics

JF - Human molecular genetics

SN - 0964-6906

IS - 17

ER -

ID: 23474524