Source:http://linkedlifedata.com/resource/pubmed/id/11689485
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
|
| pubmed:dateCreated |
2001-11-5
|
| pubmed:abstractText |
A high level of polycystin-1 expression is detected in kidneys of all patients with autosomal dominant polycystic kidney disease (ADPKD). Mice that overexpress polycystin-1 also develop renal cysts. Whether overexpression of polycystin-1 is necessary for cyst formation is still unclear. Here, we report the generation of a targeted mouse mutant with a null mutation in Pkd1 and its phenotypic characterization in comparison with the del34 mutants that carry a 'truncation mutation' in Pkd1. We show that null homozygotes develop the same, but more aggressive, renal and pancreatic cystic disease as del34/del34. Moreover, we report that both homozygous mutants develop polyhydramnios, hydrops fetalis, spina bifida occulta and osteochondrodysplasia. Heterozygotes also develop adult-onset pancreatic disease. We show further that del34 homozygotes continue to produce mutant polycystin-1, thereby providing a possible explanation for increased immunoreactive polycystin-1 in ADPKD cyst epithelia in the context of the two-hit model. Our data demonstrate for the first time that loss of polycystin-1 leads to cyst formation and defective skeletogenesis, and indicate that polycystin-1 is critical in both epithelium and chondrocyte development.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0964-6906
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
10
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2385-96
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| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:11689485-Animals,
pubmed-meshheading:11689485-Bone Diseases,
pubmed-meshheading:11689485-Disease Progression,
pubmed-meshheading:11689485-Embryo, Mammalian,
pubmed-meshheading:11689485-Female,
pubmed-meshheading:11689485-Heterozygote,
pubmed-meshheading:11689485-Homozygote,
pubmed-meshheading:11689485-Hydrops Fetalis,
pubmed-meshheading:11689485-Male,
pubmed-meshheading:11689485-Mice,
pubmed-meshheading:11689485-Mice, Inbred BALB C,
pubmed-meshheading:11689485-Mice, Inbred C3H,
pubmed-meshheading:11689485-Mice, Inbred C57BL,
pubmed-meshheading:11689485-Mice, Inbred Strains,
pubmed-meshheading:11689485-Mice, Knockout,
pubmed-meshheading:11689485-Mutation,
pubmed-meshheading:11689485-Pancreatic Cyst,
pubmed-meshheading:11689485-Pancreatic Diseases,
pubmed-meshheading:11689485-Phenotype,
pubmed-meshheading:11689485-Polycystic Kidney Diseases,
pubmed-meshheading:11689485-Polyhydramnios,
pubmed-meshheading:11689485-Pregnancy,
pubmed-meshheading:11689485-Proteins,
pubmed-meshheading:11689485-TRPP Cation Channels
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects.
|
| pubmed:affiliation |
Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
|