Document Detail

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin.
MedLine Citation:
PMID:  21502335     Owner:  NLM     Status:  MEDLINE    
Preterm premature rupture of membranes is responsible for one-third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. In particular, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn(-/-)Dcn(-/-)) mice demonstrate phenotypic changes similar to EDS, we used this model to test whether either biglycan or decorin or both play a role in the attainment of successful term gestation. Wild-type biglycan null mutant, decorin null mutant, and biglycan/decorin null mutant pregnancies were assessed for the length of gestation, pup and placenta weight, and litter size. Quantitative real-time PCR was performed to measure biglycan and decorin gene expression, and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic days E12, E15, and E18. Bgn(-/-)Dcn(-/-) dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. The number of Bgn(-/-)Dcn(-/-) pups was decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in the absence of each other and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose-dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.
Megan L Calmus; Elyse E Macksoud; Richard Tucker; Renato V Iozzo; Beatrice E Lechner
Related Documents :
15072735 - The effect of the family case management program on 1996 birth outcomes in illinois.
23046825 - Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amn...
10469765 - Cardiopulmonary resuscitation in the very low birth weight infant: the vermont oxford n...
8515305 - Orogastric tube insertion length in very low birth weight infants.
23897635 - Palivizumab prophylaxis during nosocomial outbreaks of respiratory syncytial virus in a...
14766445 - Fetal cortisol in relation to labour, intrapartum events and mode of delivery.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-04-18
Journal Detail:
Title:  Reproduction (Cambridge, England)     Volume:  142     ISSN:  1741-7899     ISO Abbreviation:  Reproduction     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-14     Completed Date:  2011-12-06     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  100966036     Medline TA:  Reproduction     Country:  England    
Other Details:
Languages:  eng     Pagination:  183-94     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Biglycan / genetics,  physiology*
Body Weight
Decorin / genetics,  physiology*
Disease Models, Animal*
Ehlers-Danlos Syndrome / metabolism,  pathology,  physiopathology,  prevention & control
Extraembryonic Membranes / embryology,  metabolism,  pathology
Fetal Development
Fetal Membranes, Premature Rupture / metabolism,  pathology,  physiopathology,  prevention & control
Gene Expression Regulation, Developmental
Litter Size
Mice, Mutant Strains
Molecular Targeted Therapy
Placenta / metabolism,  pathology
Pregnancy Proteins / genetics,  physiology*
Premature Birth / metabolism,  pathology,  physiopathology*,  prevention & control
RNA, Messenger / metabolism
Grant Support
1K08HD054676/HD/NICHD NIH HHS; 5P20RR018728-08/RR/NCRR NIH HHS; K08 HD054676/HD/NICHD NIH HHS; K08 HD054676-01A2/HD/NICHD NIH HHS; R01CA39481/CA/NCI NIH HHS
Reg. No./Substance:
0/Bgn protein, mouse; 0/Biglycan; 0/Dcn protein, mouse; 0/Decorin; 0/Pregnancy Proteins; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  In vitro growth and steroidogenesis of dog follicles are influenced by the physical and hormonal mic...
Next Document:  Behavioral specifications of reward-associated long-term memory enhancement in humans.