Chloride channels in the kidney: lessons learned from knockout animals

Area of Science:

• Molecular biology
• Nephrology
• Physiology

Background:

• Chloride (Cl-) channels are crucial for cellular functions like volume regulation, pH balance, and epithelial transport.
• Many Cl- channels in the kidney have been characterized by their biophysical properties, but their molecular identities often remain unknown.
• Understanding Cl- channel function is vital for comprehending kidney physiology and associated diseases.

Purpose of the Study:

• To review the role of gene-targeted mouse models in understanding kidney Cl- channel function.
• To focus on disruptions in the CLC family and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channels.
• To highlight the utility of these models for studying inherited kidney diseases and cystic fibrosis.

Main Methods:

• Review of existing literature on gene-targeted mouse models.
• Focus on mouse models with disrupted CLC family genes and the CFTR gene.
• Analysis of phenotypes associated with these genetic disruptions in the kidney.

Main Results:

• Disruption of CLC family members in mice has yielded models for kidney diseases like Dent's disease and diabetes insipidus.
• Mice with disrupted CFTR serve as models for cystic fibrosis, though they lack overt renal phenotypes.
• Studies in CFTR knockout mice illuminate the role of CFTR in the kidney and the significance of alternative Cl- pathways.

Conclusions:

• Gene-targeted mouse models, particularly for CLC and CFTR channels, are invaluable for studying kidney Cl- channelopathies.
• These models aid in understanding inherited kidney diseases and the complex roles of Cl- channels.
• The importance of compensatory Cl- pathways is underscored in Cl- channel knockout models.