Transcriptional profiling of the megabladder mouse: a unique model of bladder dysmorphogenesis.
Recent studies in our lab identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb-/-) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion/translocation into chromosomes 11 and 16. Transcriptional profiling identified a significantly over-expressed cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb-/- bladders. Pathway analysis of mgb microarray data indicated dysregulation of at least 60 gene products associated with smooth muscle development. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb-/- bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development.
Singh
Sunita
S
Center for Cell and Developmental Biology, Columbus Children's Research Institute, Columbus, Ohio 43205, USA.
Robinson
Melissa
M
Ismail
Ihab
I
Saha
Monalee
M
Auer
Herbert
H
Kornacker
Karl
K
Robinson
Michael L
ML
Bates
Carlton M
CM
McHugh
Kirk M
KM
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics; D009130:Muscle, Smooth / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D001743:Urinary Bladder / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*
D036361:Peptide Hormones; D026362:Serum Response Factor; C503205:urotensin II-related peptide, mouse