Following the Expression of a Kidney-Specific Gene from Early Development to Adulthood

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Abstract

Ksp-cadherin (Cadherin 16) is a unique, tissue-specific member of the cadherin family of cell adhesion proteins that is expressed exclusively in tubular epithelial cells in the adult kidney and developing genitourinary (GU) tract. Since its original identification in 1995, Ksp-cadherin has proven to be a useful experimental model for studies of kidney-specific and developmental gene regulation. These investigations have led to the creation of new strains of transgenic mice that will be useful for studies of renal cell lineage and tissue-specific gene targeting. Recent studies have also identified Ksp-cadherin as the first kidney-specific promoter that it is regulated by HNF-1β (hepatocyte nuclear factor-1β), a transcription factor that has been implicated in human renal cystic disease.

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Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease.

M Bulman, Brett Allen, Ian A. Nicholls … (2001)

Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with early-onset diabetes and nondiabetic renal disease-particularly renal cystic disease. We investigated a possible role for the HNF-1beta gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1beta gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1beta mutations.

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Isolation and cDNA cloning of Ksp-cadherin, a novel kidney-specific member of the cadherin multigene family.

R B Thomson, P Igarashi, D Biemesderfer … (1995)

Cadherins are recognized as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. We report here the identification of a structurally unique, kidney-specific member of the cadherin multigene family (Ksp-cadherin). cDNA cloning and molecular analysis of the 130-kDa protein confirmed that it was novel and indicated that it most closely resembled members of the LI-cadherin/HPT-1 cadherin subgroup. The predicted protein possesses the definitive cadherin-specific sequence motifs LDRE, DXND, and DXD in well conserved sequential arrangement, and the characteristic cysteine residues found in the last ectodomains of almost all known cadherins. Like LI-cadherin and HPT-1, Ksp-cadherin lacks the prosequence and HAV adhesion recognition sequence typical of most classical cadherins, and possesses a truncated cytoplasmic domain (18-22 amino acids). When expressed in a transient Vaccinia/T7 expression system, Ksp-cadherin displayed the classic calcium sensitivity to trypsin proteolysis that is observed in all cadherins. Immunolocalization studies and Northern analysis indicated that expression of Ksp-cadherin was kidney-specific and limited to the basolateral membranes of renal tubular epithelial cells. In summary, we have identified and cloned a novel, kidney-specific member of the cadherin multigene family that we propose be designated Ksp-cadherin.

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Cadherin-17 is required to maintain pronephric duct integrity during zebrafish development.

Julia Horsfield, Anassuya Ramachandran, Katja Reuter … (2002)

We have isolated a zebrafish cadherin that is orthologous to human LI-cadherin (CDH17). Zebrafish cdh17 is expressed exclusively in the pronephric ducts during embryogenesis, and in the mesonephros during larval development and adulthood. Like its mammalian ortholog, cdh17 is also expressed in liver and intestine in adult zebrafish. We show that cdh17-positive mesodermal cells do not contribute to the hematopoietic system. Consistent with a cell adhesion role for Cdh17, depletion of Cdh17 function using antisense morpholino oligonucleotides compromised cell cohesion during pronephric duct formation. Our results indicate that Cdh17 is necessary for maintaining the integrity of the pronephric ducts during zebrafish embryogenesis. This finding contrasts with the role of mammalian CDH17, which does not appear to be involved in nephric development.

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Journal

Journal ID (publisher-id): NEE

Journal ID (nlm-ta): Nephron Exp Nephrol

Journal ID (doi): 10.1159/issn.1660-2129

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISSN (Electronic): 1660-2129

Publication date Subscription-year: 2003

Publication date (Print): May 2003

Publication date (Electronic): 17 November 2004

Volume: 94

Issue: 1

Pages: e1-e6

Affiliations

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex., USA

Article

Publisher ID: 70812 Other ID: Nephron Exp Nephrol 2003;94:e1–e6

DOI: 10.1159/000070812

PubMed ID: 12806181

SO-VID: d4ca83e2-dc9f-4f87-8d4a-85041d7f7c91

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Following the Expression of a Kidney-Specific Gene from Early Development to Adulthood

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Abstract

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Karger: Nephrology

Most cited references 5

Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease.

Isolation and cDNA cloning of Ksp-cadherin, a novel kidney-specific member of the cadherin multigene family.

Cadherin-17 is required to maintain pronephric duct integrity during zebrafish development.

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