PMID- 21042780
OWN - NLM
STAT- MEDLINE
DCOM- 20110308
LR  - 20190606
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 26
IP  - 6
DP  - 2010 Dec
TI  - p63 (TP73L) a key player in embryonic urogenital development with significant 
      dysregulation in human bladder exstrophy tissue.
PG  - 861-7
AB  - Human bladder exstrophy-epispadias complex (BEEC) comprises a spectrum of 
      urogenital anomalies in which part or all of the distal urinary tract fails to 
      close. Several lines of evidence implicate genetic factors in the formation of 
      BEEC. Among them a murine p63+/+ knockout model showed the full picture of 
      classic exstrophy of the bladder and other urogenital defects within the BEEC 
      spectrum. This led us to study in depth the role of p63 in urogenital development 
      in mice and investigate the implication of p63 in human BEEC. Whole mount in situ 
      analysis in mice was carried out to investigate the ventro-caudal expression of 
      the p63 transcript at gestational days (GD) 9.5-12.5, the equivalent of human 
      gestational weeks 4-6 (postulated time of BEEC organogenesis in humans). In 
      addition, p63 expression analysis was performed in human blood and bladder 
      derived samples of 15 BEEC newborns accompanied by sequencing analysis of their 
      genomic DNA. We also conducted sequencing analysis of genomic DNA in additional 
      22 BEEC patients. In mouse embryos, p63 expression was detected at days 9.5-12.5 
      in the cloacal membrane and urethral epithelium, supporting its role in the 
      morphogenesis of the external genitalia and the bladder. Tissue-specific 
      expression of a novel and already-known mRNA isoforms were established and a 
      reproducible dysregulation of variable p63 isoforms was observed in 11 of 15 
      patients indicating altered gene expression. However, no obvious p63 gene 
      mutations were identified in any of the patients. Our findings strongly suggest 
      that p63 is not only involved in embryonic formation of the urogenital and 
      ventrocaudal anatomy but is also highly dysregulated in human BEEC bladder 
      tissue. Since p63 has been shown to self-regulate its expression through a 
      balance of its isoforms, the dysregulation observed may contribute to the 
      formation of BEEC.
FAU - Ching, Bonnie J
AU  - Ching BJ
AD  - Section of Genetics, Department of Pediatrics, University of California-Davis, 
      Sacramento, CA 95817, USA.
FAU - Wittler, Lars
AU  - Wittler L
FAU - Proske, Judith
AU  - Proske J
FAU - Yagnik, Garima
AU  - Yagnik G
FAU - Qi, Lihong
AU  - Qi L
FAU - Draaken, Markus
AU  - Draaken M
FAU - Reutter, Heiko
AU  - Reutter H
FAU - Gearhart, John P
AU  - Gearhart JP
FAU - Ludwig, Michael
AU  - Ludwig M
FAU - Boyadjiev, Simeon A
AU  - Boyadjiev SA
LA  - eng
GR  - M01-RR00052/RR/NCRR NIH HHS/United States
GR  - R01 DE016886/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (TP63 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Animals
MH  - Bladder Exstrophy/embryology/*metabolism
MH  - Epispadias/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - In Situ Hybridization
MH  - Lymphocytes/metabolism
MH  - Mice
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - Urinary Bladder/embryology/metabolism
EDAT- 2010/11/03 06:00
MHDA- 2011/03/09 06:00
CRDT- 2010/11/03 06:00
PHST- 2010/11/03 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/03/09 06:00 [medline]
AID - 10.3892/ijmm_00000535 [doi]
PST - ppublish
SO  - Int J Mol Med. 2010 Dec;26(6):861-7. doi: 10.3892/ijmm_00000535.