Analysis Tools
mortality/aging
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• only 1 out of 400 homozygotes survived the neonatal period and died at P8 with pale cystic kidneys and a cystic pancreas
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• after E18.5, most mutant embryos are dead, partly absorbed or misshapen
• few homozygotes survive to term but die, on average, 4 hours after birth
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cardiovascular system
| N |
• homozygotes exhibit normal fetal hearts relative to wild-type mice
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digestive/alimentary system
|
• homozygotes show early and massive dilatation of pancreatic ducts
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endocrine/exocrine glands
| N |
• homozygotes exhibit no cyst formation in testis, ovary or salivary glands
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• homozygotes show early and massive dilatation of pancreatic ducts
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• homozygotes contain fewer islets of Langerhans than wild-type mice; in contrast, acini appear to develop normally
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pancreas cyst
(
J:43193
)
|
• homozygotes exhibit cysts in major pancreatic ducts as early as E13.5, before renal cysts develop
• newborn (and P8) pancreases contain massive yellow fluid-filled cysts that enlarge with age
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growth/size/body
pancreas cyst
(
J:43193
)
|
• homozygotes exhibit cysts in major pancreatic ducts as early as E13.5, before renal cysts develop
• newborn (and P8) pancreases contain massive yellow fluid-filled cysts that enlarge with age
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• homozygotes that die perinatally first exhibit tubular and periglomerular cysts at E15.5; no histological abnormalities are noted until E14.5
(J:43193)
• the number and size of cysts increase with age
(J:43193)
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|
• after E15.5, progressive tubule dilatation and cyst formation is noted in mutant cortex
• in newborn homozygotes, epithelial cysts occupy most of the cortex
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• at E15.5, tubular and periglomerular cysts are scattered throughout the outer medulla; nephrogenesis at the rim of the kidney remains unaffected
• cyst formation is subsequently noted in collecting tubules of the inner medulla
• in newborn homozygotes, epithelial cysts occupy the entire medulla
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• at P8, the sole mutant survivor is significantly smaller relative to wild-type
(J:43193)
• newborn homozygotess exhibit dwarfism relative to newborn wild-type mice
(J:72627)
|
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• homozygotes that die perinatally display distended abdomens
|
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• homozygotes that die perinatally exhibit massive kidney enlargement
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hematopoietic system
| N |
• homozygotes display no changes in hemoglobin levels or erythrocyte morphology relative to wild-type
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homeostasis/metabolism
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• exhibit mild hydrops fetalis at late stages of fetal development
|
skin edema
(
J:72627
)
|
• histologically, mutant fetuses exhibit a mild subcutaneous edema
|
|
• exhibit mild polyhydramnios at late stages of fetal development
|
liver/biliary system
| N |
• unlike patients with ADPKD, homozygotes display no liver cyst formation
|
renal/urinary system
| N |
• in mutants, the initial stages of lumen formation and tubule differentiation proceed normally as late as E15.5
|
|
• in culture, kidney epithelial cells isolated from E15.5 (pre-cystic) mutant mice form primary cilia but fail to increase Ca2+ influx in response to physiological fluid flow at low levels of fluid shear stress (0.75 dyne cm-2)
• no Ca2+ signaling is detected in wild-type or mutant cells at higher levels of fluid shear stress (15 dyne cm-2)
• both wild-type and mutant cells respond to thrombin by increasing cytosolic Ca2+ concentrations, indicating that mutant cells retain the ability to conduct Ca2+ but lose the ability to sense fluid flow
• the Ca2+ response to thrombin is enhanced in mutant cells relative to wild-type cells, either in the presence of extracellular Ca2+
|
|
• homozygotes that die perinatally first exhibit tubular and periglomerular cysts at E15.5; no histological abnormalities are noted until E14.5
(J:43193)
• the number and size of cysts increase with age
(J:43193)
|
|
• after E15.5, progressive tubule dilatation and cyst formation is noted in mutant cortex
• in newborn homozygotes, epithelial cysts occupy most of the cortex
|
|
• at E15.5, tubular and periglomerular cysts are scattered throughout the outer medulla; nephrogenesis at the rim of the kidney remains unaffected
• cyst formation is subsequently noted in collecting tubules of the inner medulla
• in newborn homozygotes, epithelial cysts occupy the entire medulla
|
|
• homozygotes that die perinatally exhibit massive kidney enlargement
|
|
• by P8, renal parencyma in the sole survivor is almost completely replaced by cysts; cuboidal tubular epithelia are replaced by flattened cyst-lining epithelia
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• at E15.5, homozygotes display progressive multifocal microdilatation of tubules in proximal tubules of the outer medulla
• in newborn homozygotes, tubule dilatation is more extensive, affecting most of the kidney
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respiratory system
|
• a number of newborn homozygotes exhibit thyroid cartilage malformation
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small lung
(
J:43193
)
|
• homozygotes that die perinatally have small lungs relative to wild-type mice
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• homozygotes that die perinatally have hypoplastic lungs
|
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• homozygotes that survive to term but die perinatally exhibit difficulty in breathing and fail to turn pink
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skeleton
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• 8 out of 11 (73%) homozygotes develop mild spina bifida occulta in the lumbar region at late embryonic or newborn stages
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• a number of newborn homozygotes exhibit thyroid cartilage malformation
|
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• newborn homozygotes display osteochondrodysplasia
|
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• newborn homozygotes display a delay in bone mineralization of vertebrae, long bones and skull relative to wild-type mice
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nervous system
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• 8 out of 11 (73%) homozygotes develop mild spina bifida occulta in the lumbar region at late embryonic or newborn stages
|
embryo
|
• 8 out of 11 (73%) homozygotes develop mild spina bifida occulta in the lumbar region at late embryonic or newborn stages
|
integument
skin edema
(
J:72627
)
|
• histologically, mutant fetuses exhibit a mild subcutaneous edema
|
cellular
|
• in culture, kidney epithelial cells isolated from E15.5 (pre-cystic) mutant mice form primary cilia but fail to increase Ca2+ influx in response to physiological fluid flow at low levels of fluid shear stress (0.75 dyne cm-2)
• no Ca2+ signaling is detected in wild-type or mutant cells at higher levels of fluid shear stress (15 dyne cm-2)
• both wild-type and mutant cells respond to thrombin by increasing cytosolic Ca2+ concentrations, indicating that mutant cells retain the ability to conduct Ca2+ but lose the ability to sense fluid flow
• the Ca2+ response to thrombin is enhanced in mutant cells relative to wild-type cells, either in the presence of extracellular Ca2+
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:43193 , J:72627 , J:81443 | |
