PMID- 17161201
OWN - NLM
STAT- MEDLINE
DCOM- 20070103
LR  - 20220316
IS  - 1531-5037 (Electronic)
IS  - 0022-3468 (Linking)
VI  - 41
IP  - 12
DP  - 2006 Dec
TI  - Sonic hedgehog, BMP4, and Hox genes in the development of anorectal malformations 
      in Ethylenethiourea-exposed fetal rats.
PG  - 2041-5
AB  - 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.
FAU - Mandhan, Parkash
AU  - Mandhan P
AD  - Department of Paediatric and Surgery, Children's Cancer and Developmental Genetic 
      Research Group, Christchurch School of Medicine & Health Sciences, Christchurch, 
      New Zealand.
FAU - Quan, Qi Bao
AU  - Quan QB
FAU - Beasley, Spencer
AU  - Beasley S
FAU - Sullivan, Michael
AU  - Sullivan M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Bmp4 protein, rat)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 24FOJ4N18S (Ethylenethiourea)
SB  - IM
MH  - Anal Canal/abnormalities
MH  - Animals
MH  - Bone Morphogenetic Protein 4
MH  - Bone Morphogenetic Proteins/genetics
MH  - Disease Models, Animal
MH  - Ethylenethiourea/*adverse effects
MH  - Female
MH  - Genes, Homeobox/genetics
MH  - Hedgehog Proteins/genetics
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rectal Diseases/*chemically induced/congenital/*genetics
MH  - Rectum/abnormalities
MH  - Signal Transduction
EDAT- 2006/12/13 09:00
MHDA- 2007/01/04 09:00
CRDT- 2006/12/13 09:00
PHST- 2006/12/13 09:00 [pubmed]
PHST- 2007/01/04 09:00 [medline]
PHST- 2006/12/13 09:00 [entrez]
AID - S0022-3468(06)00565-3 [pii]
AID - 10.1016/j.jpedsurg.2006.08.035 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2006 Dec;41(12):2041-5. doi: 10.1016/j.jpedsurg.2006.08.035.