Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and Cystogenesis

Area of Science:

• Nephrology
• Renal Physiology
• Cilia Biology

Background:

• The role of primary cilia in regulating kidney function and blood pressure (BP) is not fully understood.
• This study investigates the consequences of losing nephron cilia on renal physiology, BP, and cyst development.

Purpose of the Study:

• To determine the impact of nephron-specific cilia loss on renal function and BP.
• To investigate the relationship between cilia disruption, cystogenesis, and BP regulation.

Main Methods:

• Mice underwent doxycycline-inducible, nephron-specific knockout (KO) of the Ift88 gene.
• Blood pressure, kidney function, and renal pathology were assessed 2 and 9 months post-knockout.
• Measurements included BP, salt-induced natriuresis, urinary nitrite and nitrate (NOx) excretion, and kidney NOS3 levels.

Main Results:

• In male mice, Ift88 KO led to reduced BP and increased urinary NOx excretion at 2 months, which was prevented by L-NAME.
• At 9 months, male Ift88 KO mice developed polycystic kidneys, elevated BP, and reduced urinary NOx excretion.
• No significant differences in BP or renal function were observed in female mice.

Conclusions:

• Nephron cilia disruption in male mice initially lowers BP, potentially due to increased nitric oxide (NO) production.
• Cilia loss ultimately induces polycystic kidneys associated with hypertension and decreased renal NO production in males.
• Sex-specific differences exist in the renal response to cilia disruption.