Glomerular and proximal tubule cysts as early manifestations of Pkd1 deletion.
BACKGROUND
The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios.


METHODS
We used Pkd1-null mice to investigate cystogenesis and analyze the amniotic fluid composition from embryonic day 12.5 (E12.5) to birth (n = 257 embryos).


RESULTS
Polyhydramnios was consistently observed from E13.5 in Pkd1(-/-) embryos, in absence of placental abnormalities but with a significantly higher excretion of sodium and glucose from E13.5 through E16.5, and increased cyclic adenosine 3'5-monophosphate (cAMP) levels at E14.5 and E15.5. The Pkd1(-/-) embryos started to die at E13.5, with lethality peaking at E15.5, corresponding to the onset of cystogenesis. The first cysts in Pkd1(-/-) kidneys emerged at E15.5 in mesenchyme-derived segments at the cortico-medullary junction, with a majority of glomerular cysts and fewer proximal tubule cysts (positive for megalin). The cysts extended to ureteric bud-derived collecting ducts (positive for Dolichos biflorus agglutinin lectin) from E16.5.


CONCLUSIONS
These studies indicate that Pkd1 deletion is associated with a massive loss of solutes (from E13.5) and increased cAMP levels (E14.5) associated with polyhydramnios. These abnormalities precede renal cysts (E15.5), first derived from glomeruli and proximal tubules and later from the collecting ducts, reflecting the expression pattern of Pkd1 in maturing epithelial cells.
Ahrabi
Ali K
AK
Division of Nephrology, Université catholique de Louvain Medical School, Brussels, Belgium.
Jouret
François
F
Marbaix
Etienne
E
Delporte
Christine
C
Horie
Shigeo
S
Mulroy
Sharon
S
Boulter
Catherine
C
Sandford
Richard
R
Devuyst
Olivier
O
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D007690:Polycystic Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D006831:Polyhydramnios / Q000175:diagnosis / Q000473:pathology; D011247:Pregnancy; D015996:Survival Rate; D050396:TRPP Cation Channels / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D000242:Cyclic AMP; D050396:TRPP Cation Channels; D001616:beta-Galactosidase