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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Prevalence and Pathologic Characterization of Mouse Kidney Parvovirus in Sentinel CD1 Mice
Zhongming Ge1, Yan Feng1, Nicola M Parry2
11Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Abstract:
Mouse kidney parvovirus (MKPV) infection can cause significant morbidity and mortality by inducing moderate to severe inclusion body nephropathy and kidney fibrosis in aged immunodeficient mice. However, MKPV infection in immunocompetent mice is associated with histopathologic findings ranging from absent to minimal or moderate lymphoplasmacytic interstitial nephritis without inclusion body in most cases. We surveyed the prevalence of MKPV via PCR from August 2019 through January 2021, using feces, kidneys, and livers collected and pooled from 2 sentinel mice [Crl:CD1(ICR)] (CD1) per surveillance cage (a total of 212 cages). CD1 mice used as dirty-bedding sentinels were housed for 6 mo in a separate cage on the same rack as colony mice used in research at the Massachusetts Institute of Technology and at the Whitehead Institute for Biomedical Research. MKPV quantitative PCR positivity was 16.04%, 14.62%, and 10.02% for feces, kidney, and liver, respectively. The aggregate prevalence of MKPV was 22.64% (48 of 212 samples). Thirty-three of 103 rooms (32.04%) were MKPV positive. MKPV-positive kidneys had more severe chronic lymphoplasmacytic interstitial nephritis (CLIN) than MKPV-negative kidneys; however, there was no significant difference in hepatic lesions between MKPV-positive and -negative livers. Although no overt intranuclear inclusion body nephropathy was noted in MKPV-positive CD1 kidneys, MKPV RNA was sporadically detected within tubular epithelial cells in MKPV-positive kidneys but not in MKPV-positive livers. Our study indicates that MKPV can be easily transmitted through soiled bedding. It highlights that CD1 mice can be used as sentinels to detect MKPV, emphasizing the importance of monitoring MKPV distribution using quantitative PCR in sentinel mice if MKPV needs to be excluded from a colony. Importantly, as MKPV infection is associated with mild to moderate CLIN, MKPV can potentially confound the interpretation of in vivo biomedical data.
Insights
Mouse kidney parvovirus (MKPV) is prevalent in research settings and easily spreads via soiled bedding. Monitoring MKPV in sentinel mice is crucial for research integrity, as it can cause kidney inflammation and affect study results.
Area of Science:
- Veterinary Pathology
- Infectious Diseases
- Animal Models
Background:
- Mouse kidney parvovirus (MKPV) causes significant kidney disease in immunodeficient mice.
- In immunocompetent mice, MKPV infection typically presents with mild interstitial nephritis without inclusion bodies.
- Understanding MKPV transmission and prevalence is vital for maintaining research colony health and data integrity.
Purpose of the Study:
- To survey the prevalence of MKPV in research mouse colonies using sentinel mice.
- To assess the association between MKPV infection and kidney histopathology in immunocompetent mice.
- To evaluate the utility of CD1 mice as sentinels for MKPV detection.
Main Methods:
- Quantitative PCR was used to detect MKPV in feces, kidneys, and livers of sentinel CD1 mice over 18 months.
- Sentinel mice were housed on the same racks as research mice to monitor environmental contamination.
- Histopathological examination of kidneys and livers was performed to correlate MKPV presence with lesions.
Main Results:
- MKPV was detected in 22.64% of sentinel mouse samples, with 32.04% of rooms testing positive.
- MKPV-positive kidneys showed significantly more severe chronic lymphoplasmacytic interstitial nephritis (CLIN) than negative controls.
- MKPV RNA was detected in tubular epithelial cells of positive kidneys, but no overt inclusion bodies were observed.
Conclusions:
- MKPV is readily transmitted via soiled bedding, and CD1 mice effectively serve as sentinels for its detection.
- MKPV infection in immunocompetent mice is associated with mild to moderate kidney inflammation (CLIN).
- MKPV presence can potentially confound the interpretation of in vivo research data, necessitating vigilant monitoring.
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