Cited1 is required in trophoblasts for placental development and for embryo growth and survival

Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors α and β, TFAP2, and CBP/p300. It is expressed in a restricted manner in the embryo as well as in extraembryonic tissues during embryonic development. In this study we report the engineering of a loss-of-function Cited...

Full description

Bibliographic Details
Main Authors: Rodriguez, T, Sparrow, D, Scott, A, Withington, S, Preis, J, Michalicek, J, Clements, M, Tsang, T, Shioda, T, Beddington, R, Dunwoodie, S
Format: Journal article
Published: American Society for Microbiology 2004
_version_ 1826272669958406144
author Rodriguez, T
Sparrow, D
Scott, A
Withington, S
Preis, J
Michalicek, J
Clements, M
Tsang, T
Shioda, T
Beddington, R
Dunwoodie, S
author_facet Rodriguez, T
Sparrow, D
Scott, A
Withington, S
Preis, J
Michalicek, J
Clements, M
Tsang, T
Shioda, T
Beddington, R
Dunwoodie, S
author_sort Rodriguez, T
collection OXFORD
description Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors α and β, TFAP2, and CBP/p300. It is expressed in a restricted manner in the embryo as well as in extraembryonic tissues during embryonic development. In this study we report the engineering of a loss-of-function Cited1 mutation in the mouse. Cited1 null mutants show growth restriction at 18.5 days postcoitum, and most of them die shortly after birth. Half the heterozygous females, i.e., those that carry a paternally inherited wild-type Cited1 allele, are similarly affected. Cited1 is normally expressed in trophectoderm-derived cells of the placenta; however, in these heterozygous females, Cited1 is not expressed in these cells. This occurs because Cited1 is located on the X chromosome, and thus the wild-type Cited1 allele is not expressed because the paternal X chromosome is preferentially inactivated. Loss of Cited1 resulted in abnormal placental development. In mutants, the spongiotrophoblast layer is irregular in shape and enlarged while the labyrinthine layer is reduced in size. In addition, the blood spaces within the labyrinthine layer are disrupted; the maternal sinusoids are considerably larger in mutants, leading to a reduction in the surface area available for nutrient exchange. We conclude that Cited1 is required in trophoblasts for normal placental development and subsequently for embryo viability.
first_indexed 2024-03-06T22:16:15Z
format Journal article
id oxford-uuid:537a38b3-4c83-4126-87ab-a86fbef07db0
institution University of Oxford
last_indexed 2024-03-06T22:16:15Z
publishDate 2004
publisher American Society for Microbiology
record_format dspace
spelling oxford-uuid:537a38b3-4c83-4126-87ab-a86fbef07db02022-03-26T16:32:07ZCited1 is required in trophoblasts for placental development and for embryo growth and survivalJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:537a38b3-4c83-4126-87ab-a86fbef07db0Symplectic Elements at OxfordAmerican Society for Microbiology2004Rodriguez, TSparrow, DScott, AWithington, SPreis, JMichalicek, JClements, MTsang, TShioda, TBeddington, RDunwoodie, SCited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors α and β, TFAP2, and CBP/p300. It is expressed in a restricted manner in the embryo as well as in extraembryonic tissues during embryonic development. In this study we report the engineering of a loss-of-function Cited1 mutation in the mouse. Cited1 null mutants show growth restriction at 18.5 days postcoitum, and most of them die shortly after birth. Half the heterozygous females, i.e., those that carry a paternally inherited wild-type Cited1 allele, are similarly affected. Cited1 is normally expressed in trophectoderm-derived cells of the placenta; however, in these heterozygous females, Cited1 is not expressed in these cells. This occurs because Cited1 is located on the X chromosome, and thus the wild-type Cited1 allele is not expressed because the paternal X chromosome is preferentially inactivated. Loss of Cited1 resulted in abnormal placental development. In mutants, the spongiotrophoblast layer is irregular in shape and enlarged while the labyrinthine layer is reduced in size. In addition, the blood spaces within the labyrinthine layer are disrupted; the maternal sinusoids are considerably larger in mutants, leading to a reduction in the surface area available for nutrient exchange. We conclude that Cited1 is required in trophoblasts for normal placental development and subsequently for embryo viability.
spellingShingle Rodriguez, T
Sparrow, D
Scott, A
Withington, S
Preis, J
Michalicek, J
Clements, M
Tsang, T
Shioda, T
Beddington, R
Dunwoodie, S
Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title_full Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title_fullStr Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title_full_unstemmed Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title_short Cited1 is required in trophoblasts for placental development and for embryo growth and survival
title_sort cited1 is required in trophoblasts for placental development and for embryo growth and survival
work_keys_str_mv AT rodriguezt cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT sparrowd cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT scotta cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT withingtons cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT preisj cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT michalicekj cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT clementsm cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT tsangt cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT shiodat cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT beddingtonr cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival
AT dunwoodies cited1isrequiredintrophoblastsforplacentaldevelopmentandforembryogrowthandsurvival