Placental insufficiency associated with loss of Cited1 causes renal medullary dysplasia.
A number of studies have shown that placental insufficiency affects embryonic patterning of the kidney and leads to a decreased number of functioning nephrons in adulthood; however, there is circumstantial evidence that placental insufficiency may also affect renal medullary growth, which could account for cases of unexplained renal medullary dysplasia and for abnormalities in renal function among infants who had experienced intrauterine growth retardation. We observed that mice with late gestational placental insufficiency associated with genetic loss of Cited1 expression in the placenta had renal medullary dysplasia. This was not caused by lower urinary tract obstruction or by defects in branching of the ureteric bud during early nephrogenesis but was associated with decreased tissue oxygenation and increased apoptosis in the expanding renal medulla. Loss of placental Cited1 was required for Cited1 mutants to develop renal dysplasia, and this was not dependent on alterations in embryonic Cited1 expression. Taken together, these findings suggest that renal medullary dysplasia in Cited1 mutant mice is a direct consequence of decreased tissue oxygenation resulting from placental insufficiency.
Sparrow
Duncan B
DB
Developmental Biology Division, Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia.
Boyle
Scott C
SC
Sams
Rebecca S
RS
Mazuruk
Bogdan
B
Zhang
Li
L
Moeckel
Gilbert W
GW
Dunwoodie
Sally L
SL
de Caestecker
Mark P
MP
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007668:Kidney / Q000196:embryology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007679:Kidney Medulla / Q000196:embryology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics*; D010920:Placenta / Q000502:physiology; D010927:Placental Insufficiency / Q000235:genetics*; D011247:Pregnancy; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; C512688:CITED1 protein, human; C102208:Cited1 protein, mouse; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors