Role of Kalirin and mouse strain in retention of spatial memory training in an Alzheimer’s disease model mouse line

• Published in: Neurobiology of aging Vol. 95; pp. 69 - 80
• Main Authors: Russo-Savage, Lillian, Rao, Vishwanatha K.S., Eipper, Betty A., Mains, Richard E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: 3xTG-AD; Barnes maze; Peptide; Peptidylglycine alpha-amidating monooxygenase; Prohormone convertase; Rotarod; Western analysis; Prohormone convertase; Rotarod; Western analysis; Barnes maze; 3xTG-AD; Peptide; Peptidylglycine alpha-amidating monooxygenase
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2020.07.006

Nontransgenic and 3xTG transgenic mice, which express mutant transgenes encoding human amyloid precursor protein (hAPP) along with Alzheimer’s disease–associated versions of hTau and a presenilin mutation, acquired the Barnes Maze escape task equivalently at 3–9 months of age. Although nontransgenics retested at 6 and 9 months acquired the escape task more quickly than naïve mice, 3xTG mice did not. Deficits in Kalirin, a multidomain protein scaffold and guanine nucleotide exchange factor that regulates dendritic spines, has been proposed as a contributor to the cognitive decline observed in Alzheimer’s disease. To test whether deficits in Kalirin might amplify deficits in 3xTG mice, mice heterozygous/hemizygous for Kalirin and the 3xTG transgenes were generated. Mouse strain, age and sex affected cortical expression of key proteins. hAPP levels in 3xTG mice increased total APP levels at all ages. Kalirin expression showed strong sex-dependent expression in C57 but not B6129 mice. Decreasing Kalirin levels to half had no effect on Barnes Maze task acquisition or retraining in 3xTG hemizygous mice. •Barnes Maze performance by C57 and 3xTG-H mice (3 & 9 months) are indistinguishable.•Retested C57 mice retain functional memory of earlier Barnes Maze testing (months).•Barnes Maze performance by 3xTG-H and 3xTG-h mice are not improved by prior testing.