Urinary protein analysis in mice lacking major urinary proteins

Area of Science:

• Biochemistry
• Genetics
• Animal Models

Background:

• Mouse urine contains major urinary proteins (MUPs), unlike human urine.
• This difference complicates using mice as models for human diseases and urinalysis.
• The accuracy of standard urinalysis dipsticks in the presence of MUPs is uncertain.

Purpose of the Study:

• To generate and characterize MUP-knockout (Mup-KO) mice.
• To compare urinary protein concentrations and composition between Mup-KO and wild-type mice.
• To assess the utility of Mup-KO mice as a model for human urinalysis.

Main Methods:

• Mup-KO mice were produced using CRISPR-Cas9 gene editing.
• Urinary protein concentrations were measured using a protein quantitation kit and dipsticks.
• Urinary protein composition was analyzed via SDS-PAGE and two-dimensional electrophoresis (2DE).

Main Results:

• Mup-KO mice showed significantly lower urinary protein concentrations (17.9 mg/dl) compared to wild-type mice (73.7 mg/dl).
• Dipstick sensitivity to MUPs was limited, indicating potential inaccuracies in standard urinalysis.
• Electrophoresis confirmed the absence of MUPs in Mup-KO mice urine, mirroring human urinary protein profiles.

Conclusions:

• Mup-KO mice lack MUPs, presenting a urinary protein profile more comparable to humans.
• These mice provide a valuable preclinical model for studying human urinalysis and related diseases.
• The findings highlight limitations of current dipstick technology for MUP-containing urine.