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Molecular and Cellular Biology, February 2003, p. 1175-1180, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1175-1180.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of the PDZK1 Gene by Homologous Recombination

Olivier Kocher,* Rinku Pal, Mark Roberts, Christine Cirovic, and Annalyn Gilchrist

Department of Pathology, Beth Israel-Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Received 19 August 2002/ Returned for modification 24 September 2002/ Accepted 19 November 2002

Proteins containing PDZ domains are involved in a large number of biological functions, including protein scaffolding, organization of ion channels, and signal transduction. We recently identified a novel PDZ domain-containing protein, PDZK1, that is selectively expressed in normal tissues, where it is associated and colocalized with MAP17, a small 17-kDa membrane-associated protein; cMOAT, an organic anion transporter implicated in multidrug resistance; and the type IIa Na/Pi cotransporter. The protein cluster formed by PDZK1, MAP17, and cMOAT is upregulated in a significant number of human carcinomas originating in the colon, breast, lung, and kidney. In order to better define the function of PDZK1 in the protein cluster and its potential role in the organization of ion channels, we generated a PDZK1 knockout mouse. While PDZK1-deficient mice developed normally, did not display any gross phenotypic abnormalities, and were fecund, lack of PDZK1 resulted in modulation of expression of selective ion channels in the kidney, as well as increased serum cholesterol levels. However, no significant redistribution of proteins known to interact with PDZK1, such as MAP17, cMOAT, and the type IIa Na/Pi cotransporter, was observed. The absence of a more significant phenotype in PDZK1-deficient mice may be due to functional compensation by other PDZ domain-containing proteins, which could be instrumental in determining the location of interacting proteins such as ion channels and other membrane-associated proteins in defined areas of the plasma membrane.

* Corresponding author. Mailing address: Department of Pathology, Beth Israel-Deaconess Medical Center, East Campus, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-3598. Fax: (617) 667-3591. E-mail: okocher{at}caregroup.harvard.edu.

Molecular and Cellular Biology, February 2003, p. 1175-1180, Vol. 23, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.4.1175-1180.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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