alexa Pkd1 inactivation induced in adulthood produces focal cystic disease.
Biochemistry

Biochemistry

Biochemistry & Physiology: Open Access

Author(s): Takakura A, Contrino L, Beck AW, Zhou J

Abstract Share this page

Abstract Autosomal dominant polycystic kidney disease, the most common monogenetic disorder, is characterized by gradual replacement of normal renal parenchyma by fluid-filled cysts. Mutations in either PKD1 or PKD2 cause autosomal dominant polycystic kidney disease. Pkd1(-/-) or Pkd2(-/-) mice develop rapid renal cystic disease and exhibit embryonic lethality; this supports the "two-hit" hypothesis, which proposes that a germline mutation in PKD1 (or PKD2) followed by a second somatic mutation later in life is responsible for the phenotype. Here, for investigation of the loss of Pkd1 at specific times of development, an inducible Pkd1-knockout mouse model was generated. Inactivation of Pkd1 in 5-wk-old mice resulted in formation of only focal renal cysts 6 to 9 wk later but in a severe polycystic phenotype nearly 1 yr later. Cysts derived from either collecting tubules or distal tubules but not from proximal tubules, which correlated with sites of Cre-mediated recombination. Inactivation of Pkd1 in 1-wk-old mice, however, resulted in massive cyst disease 6 wk later, despite a similar pattern of Cre-mediated recombination between 1- and 5-wk-old kidneys. Moreover, a germline heterozygous Pkd1 mutation facilitated cyst formation when a somatic Pkd1 mutation was induced. A marked increase in proliferating cell nuclear antigen expression was observed in cyst-lining epithelia and in normal-looking tubules adjacent to but not in those distant from cysts. These data suggest that Pkd1 inactivation is not sufficient to initiate the cell proliferation necessary for cyst formation; a paracrine mechanism may account for focal cell proliferation and regional disease progression. We propose that an additional genetic or nongenetic "third hit" may be required for rapid development of cysts in polycystic kidney disease.
This article was published in J Am Soc Nephrol and referenced in Biochemistry & Physiology: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords