Distinct patterns of kidney and liver cyst growth in pkd2(WS25/-) mice

Area of Science:

• Biomedical research
• Genetics
• Animal models

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder causing cystic kidneys and liver.
• Pkd2(WS25/-) mice serve as a crucial genetic model for human ADPKD, reflecting its 'molecular recessive' inheritance.
• This study characterizes long-term cyst growth patterns in male and female Pkd2(WS25/-) mice.

Purpose of the Study:

• To document and analyze long-term cyst growth in the kidneys and liver of male and female Pkd2(WS25/-) mice.
• To establish a foundation for future long-term investigations into ADPKD.
• To compare cystogenesis patterns between sexes in this ADPKD mouse model.

Main Methods:

• Utilized gravimetric measurements to track kidney and liver growth over 12 months.
• Optimized and validated fast imaging with steady-state precision-magnetic resonance imaging (FISP-MRI) for organ and cyst volume assessment.
• Conducted longitudinal FISP-MRI analyses of cyst volume changes over 15 months.

Main Results:

• Both male and female Pkd2(WS25/-) mice showed significant kidney weight increases up to 4 months, with minimal progression thereafter.
• Liver cyst growth was minimal in males before 4 months but accelerated after 8 months.
• Females also exhibited accelerated liver growth, but with a delayed onset compared to males.

Conclusions:

• Pkd2(WS25/-) mice effectively model early kidney cyst development in human ADPKD.
• Male Pkd2(WS25/-) mice demonstrate a late-onset liver growth pattern consistent with human ADPKD patients.
• Sex-specific differences in cyst growth progression are evident in this ADPKD mouse model.