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 alpha and beta, 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.
Rodriguez
Tristan A
TA
Mammalian Development Division, National Institute for Medical Research, London, United Kingdom.
Sparrow
Duncan B
DB
Scott
Annabelle N
AN
Withington
Sarah L
SL
Preis
Jost I
JI
Michalicek
Jan
J
Clements
Melanie
M
Tsang
Tania E
TE
Shioda
Toshi
T
Beddington
Rosa S P
RS
Dunwoodie
Sally L
SL
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D004303:Dosage Compensation, Genetic; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005804:Genes, Lethal; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000196:embryology* / Q000473:pathology; D015534:Trans-Activators; D014327:Trophoblasts / Q000378:metabolism*; D014960:X Chromosome / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C102208:Cited1 protein, mouse; D009687:Nuclear Proteins; D015534:Trans-Activators