Comprehensive phenotyping profiling of chronic wasting disease to assess transmissibility and species barriers

This research program focuses on understanding Chronic Wasting Disease (CWD) through transgenic mouse models, genetic surveillance of wild cervids and investigations into potential human transmissibility. Grounded in veterinary clinical experience and prion disease research, the Grindeland laboratory combines transgenic model characterization with field-relevant genetic analyses to address critical gaps in CWD detection, susceptibility, and cross-species risk. The laboratory’s work targets two complementary objectives: establishing comprehensive phenotypic profiling of cervid PRNP polymorphisms in transgenic CWD mouse models, and examining CWD zoonosis using humanized gene-targeted mice through thorough phenotypic characterization.

To support these aims, the lab leverages expertise in transgenic models to recapitulate CWD and to map early neuropathological timepoints that could translate into earlier diagnostic approaches and more timely therapeutic interventions. Studies in mouse models that mirror CWD pathogenesis are being used to identify earlier, reliable, and humane live-testing methods suitable for both research and potential field application. A major strand of the research focuses on genetic risk factors in Montana’s wild cervid populations.

Working with Montana Fish, Wildlife & Parks, the Grindeland lab is determining the distribution of CWD-related prion protein genetics in mule deer, white-tailed deer, and elk across the state. The team analyzes samples spanning from the initial year CWD was identified in Montana through the present, seeking to identify genetic factors that influence susceptibility, disease severity, and progression. Understanding whether partially resistant genotypes are present or becoming more common can inform wildlife management strategies, including region-specific hunting pressure adjustments and other interventions aimed at limiting disease spread. Early disease identification represents another pillar of the program. Recognizing that practical limitations hinder early detection in living animals, the lab uses transgenic mouse modeling to pinpoint the earliest molecular, cellular, and behavioral markers of CWD. Investigations include blood-based markers indicative of brain and muscle damage, behavioral markers tracking cognitive impairment, and peripheral assessments in lymph nodes and spleen.

Noninvasive sample types such as feces and urine are also under investigation for their potential utility in live animal testing, hunter-facing diagnostics, and environmental contamination monitoring. The lab emphasizes humane approaches and translational potential for wildlife management and therapeutic timing. Given the unresolved question of human susceptibility to CWD, the Grindeland laboratory pursues careful investigations into zoonotic potential using sensitive phenotypic assays in humanized gene-targeted mice. This work aims to detect prion characteristics and disease markers that might not have been observed previously, using in-depth screening of multiple sensitive endpoints.

Through integrated field genetics, transgenic modeling, and development of early diagnostic tools, Andrea Grindeland’s program seeks to advance understanding of CWD transmissibility, species barriers, and practical strategies for disease management.