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Updated: Mar 21, 2026
Assessing Burrowing, Nest Construction, and Hoarding in Mice
Published on: January 5, 2012
Impaired burrowing is the most prominent behavioral deficit of aging htau mice
Philippine Camilla Geiszler1, Matthew Richard Barron1, Marie-Christine Pardon1
1Neuroscience Group, School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom.
Abstract:
htau mice are deficient of murine tau but express all six human tau isoforms, leading to gradual tau misprocessing and aggregation in brain areas relevant to Alzheimer's disease. While histopathological changes in htau mice have been researched in the past, we focused here on functional consequences of human tau accumulation. htau mice and their background controls - murine tau knock-out (mtau(-/-)) and C57Bl/6J mice - underwent a comprehensive trial battery to investigate species-specific behavior, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory as well as acquisition, retention and extinction of contextual fear at two, four, six, nine and twelve months of age. In htau mice, tau pathology was already present at two months of age, whereas deficits in food burrowing and spatial working memory were first noted at four months of age. At later stages the presence of human tau on a mtau(-/-) background appeared to guard cognitive performance; as mtau(-/-) but not htau mice differed from C57Bl/6J mice in the food burrowing, spontaneous alternation and object discrimination tasks. Aging mtau(-/-) mice also exhibited increased body mass and locomotor activity. These data highlight that reduced food-burrowing performance was the most robust aspect of the htau phenotype with aging. htau and mtau(-/-) deficits in food burrowing pointed at the necessity of intact tau systems for daily life activities. While some htau and mtau(-/-) deficits overlap, age differences between the two genotypes may reflect distinct functional effects and compared to C57Bl/6J mice, the htau phenotype appeared stronger than the mtau(-/-) phenotype at young ages but milder with aging.
Insights
Human tau accumulation in htau mice impairs daily activities like food burrowing, with deficits appearing early. The murine tau knockout model shows distinct age-related changes compared to htau mice.
Area of Science:
- Neuroscience
- Genetics
- Alzheimer's Disease Research
Background:
- htau mice express human tau isoforms, enabling study of tauopathy relevant to Alzheimer's disease.
- Previous research focused on histopathology; this study investigates functional consequences of human tau accumulation.
Purpose of the Study:
- To comprehensively assess the functional consequences of human tau accumulation in htau mice across various behavioral domains.
- To compare the behavioral phenotype of htau mice with murine tau knockout (mtau(-/-)) and wild-type (C57Bl/6J) controls at multiple ages.
Main Methods:
- A comprehensive behavioral trial battery was administered to htau, mtau(-/-), and C57Bl/6J mice at 2, 4, 6, 9, and 12 months of age.
- Tests included assessments of species-specific behavior, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory, and contextual fear conditioning.
Main Results:
- Tau pathology was present in htau mice by 2 months; functional deficits in food burrowing and spatial working memory emerged by 4 months.
- Reduced food burrowing was the most consistent phenotype in aging htau mice, indicating impaired daily life activities.
- While both htau and mtau(-/-) mice showed deficits, their age-related progression and specific cognitive impacts differed, with htau showing a stronger early phenotype and milder late phenotype compared to mtau(-/-).
Conclusions:
- Intact tau systems are crucial for daily life activities, as evidenced by food burrowing deficits in both htau and mtau(-/-) mice.
- The htau mouse model exhibits distinct functional consequences of human tau accumulation, providing insights into Alzheimer's disease pathogenesis.
- Age-dependent behavioral differences between htau and mtau(-/-) mice suggest distinct roles of murine versus human tau in cognitive function and behavior.
