RGD Reference Report - Sonic hedgehog, BMP4, and Hox genes in the development of anorectal malformations in Ethylenethiourea-exposed fetal rats. - Rat Genome Database

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Sonic hedgehog, BMP4, and Hox genes in the development of anorectal malformations in Ethylenethiourea-exposed fetal rats.

Authors: Mandhan, P  Quan, QB  Beasley, S  Sullivan, M 
Citation: Mandhan P, etal., J Pediatr Surg. 2006 Dec;41(12):2041-5.
RGD ID: 1599527
Pubmed: PMID:17161201   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jpedsurg.2006.08.035   (Journal Full-text)

BACKGROUND: shh signaling pathway has been shown to be involved in the morphogenesis of many organ systems. In this study, we investigated the expression of shh and its targets, BMP4 and Hox genes, in the development of anorectal malformations in Ethylenethiourea (ETU)-exposed embryos. METHODS: We used ETU murine model of the vertebral, anal, cardiac, tracheoesophageal, renal, and limb association. Ethylenethiourea 1% (125 mg/kg) was given to the pregnant females via gavage feeding on gestational day (gD) 10 and saline to control animals. Embryos were collected at gD12 to gD16 and gD21; hindguts were dissected and snap frozen. Highly purified RNA was isolated, and expression of shh, BMP4, Hoxa13, and Hoxd13 genes was confirmed with RT-PCR. Relative quantitative expression of shh and target genes at each time point was done with SYBR Green I qPCR. Normalized gene of interest expression was calculated by geNorm, and data analysis was done with 2-tail Student t test. RESULTS: shh, BMP4, Hoxa13, and Hoxd13 transcripts were detected in all samples, confirming that shh cascade is active during the process of hindgut development in fetal rats. Relative quantitation demonstrated that shh cascade expression shows time-dependent changes in the developing hindgut. CONCLUSION: This study shows that ETU disturbs the expression of shh signaling pathway during the development of hindgut. We provide evidence that shh plays a pivotal role in the hindgut morphogenesis, and its misexpression affect the expression of targets, BMP4 and Hox genes.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP4HumanAnorectal Malformations  ISOBmp4 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
Bmp4RatAnorectal Malformations  IEP mRNA:decreased expression:hindgutRGD 
Bmp4MouseAnorectal Malformations  ISOBmp4 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
HOXA13HumanAnorectal Malformations  ISOHoxa13 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
HOXD13HumanAnorectal Malformations  ISOHoxd13 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
Hoxa13MouseAnorectal Malformations  ISOHoxa13 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
Hoxa13RatAnorectal Malformations  IEP mRNA:decreased expression:hindgutRGD 
Hoxd13RatAnorectal Malformations  IEP mRNA:decreased expression:hindgutRGD 
Hoxd13MouseAnorectal Malformations  ISOHoxd13 (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
SHHHumanAnorectal Malformations  ISOShh (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 
ShhRatAnorectal Malformations  IEP mRNA:decreased expression:hindgutRGD 
ShhMouseAnorectal Malformations  ISOShh (Rattus norvegicus)mRNA:decreased expression:hindgutRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hoxa13Ratembryonic hindgut morphogenesis  IMP  RGD 
Hoxd13Ratembryonic hindgut morphogenesis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp4  (bone morphogenetic protein 4)
Hoxa13  (homeo box A13)
Hoxd13  (homeo box D13)
Shh  (sonic hedgehog signaling molecule)

Genes (Mus musculus)
Bmp4  (bone morphogenetic protein 4)
Hoxa13  (homeobox A13)
Hoxd13  (homeobox D13)
Shh  (sonic hedgehog)

Genes (Homo sapiens)
BMP4  (bone morphogenetic protein 4)
HOXA13  (homeobox A13)
HOXD13  (homeobox D13)
SHH  (sonic hedgehog signaling molecule)


Additional Information