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Gene expression profiling of constitutive activation of Smoothened in the mouse uterus


ABSTRACT: In order to gain a better understanding of Ihh action during embryo implantation, we constitutively activated Smo in the murine uterus using the PRcre mouse model (PRcre/+SmoM2+; SmoM2). Female SmoM2 mice were infertile. They exhibited normal serum progesterone levels and normal ovulation, but ova failed to be fertilized in vivo and the uterus failed to undergo the artificially induced decidual response. SmoM2 mice exhibited uterine hypertrophy. The endometrium had a reduced number of uterine glands and the endometrial stroma lost its normal morphologic characteristics. Microarray analysis of 3 month old SmoM2 uteri demonstrated a chondrocytic signature and confirmed that constitutive activation of SmoM2 increased extracellular matrix production. Thus, constitutive activation of Smo in the mouse uterus alters the extracellular matrix which interferes with early pregnancy. Keywords: two group comparison We constitutively activated Hh signaling in the uterus by the expression of a mutant SmoM2 allele. We crossed these mice to the PRcre mouse model to constitutively activate Smo in the murine uterus (PRcre/+SmoM2+; SmoM2). High density DNA microarray analysis was performed on 3 month old control and SmoM2 uteri.

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton 

PROVIDER: E-GEOD-17263 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Constitutive activation of smoothened leads to female infertility and altered uterine differentiation in the mouse.

Franco Heather L HL   Lee Kevin Y KY   Rubel Cory A CA   Creighton Chad J CJ   White Lisa D LD   Broaddus Russell R RR   Lewis Michael T MT   Lydon John P JP   Jeong Jae-Wook JW   DeMayo Francesco J FJ  

Biology of reproduction 20100203 5


Previous work has identified Indian hedgehog (Ihh) as a major mediator of progesterone signaling during embryo implantation. Ihh acts through its downstream effector smoothened (Smo) to activate the GLI family of transcription factors. In order to gain a better understanding of Ihh action during embryo implantation, we expressed a Cre-recombinase-dependent constitutively activated SMO in the murine uterus using the Pgr(tm2(cre)Lyd) (PR(cre)) mouse model [Pgr(tm2(cre)Lyd+)Gt(ROSA)26Sor(tm1(Smo/EY  ...[more]

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