Generation of a New Tau Knockout (tauΔex1) Line Using CRISPR/Cas9 Genome Editing in Mice.

Alzheimer's disease and other dementias present with tau pathology. Several mouse lines with knockout of the tau-encoding Mapt gene have been reported, yet findings often differed between lines and sites. Here, we report a new tau knockout strain (tauΔex1), generated by CRISPR/Cas9-mediated genome editing of intron -1/exon 1 of Mapt in C57Bl/6J mice. TauΔex1 mice had no overt phenotype, but, in line with previous models, they showed a significantly reduced susceptibility to excitotoxic seizures, with normal memory formation in young mice. This new in vivo resource will be made freely available to the research community.

[1]  T. Fath,et al.  Tau exacerbates excitotoxic brain damage in an animal model of stroke , 2017, Nature Communications.

[2]  L. Buée,et al.  Tau deletion promotes brain insulin resistance , 2017, The Journal of experimental medicine.

[3]  L. Ittner,et al.  Generation of Genetically Modified Mice through the Microinjection of Oocytes. , 2017, Journal of visualized experiments : JoVE.

[4]  A. Ittner SITE-SPECIFIC PHOSPHORYLATION OF TAU INHIBITS AMYLOID-β TOXICITY IN ALZHEIMER’S MICE , 2016, Alzheimer's & Dementia.

[5]  Y. Li,et al.  Insertion of a knockout-first cassette in Ampd1 gene leads to neonatal death by disruption of neighboring genes expression , 2016, Scientific Reports.

[6]  A. Bongers,et al.  No Overt Deficits in Aged Tau-Deficient C57Bl/6.Mapttm1(EGFP)Kit GFP Knockin Mice , 2016, PloS one.

[7]  G. Halliday,et al.  Short-term suppression of A315T mutant human TDP-43 expression improves functional deficits in a novel inducible transgenic mouse model of FTLD-TDP and ALS , 2015, Acta Neuropathologica.

[8]  E. Teng,et al.  Loss of MAP Function Leads to Hippocampal Synapse Loss and Deficits in the Morris Water Maze with Aging , 2014, The Journal of Neuroscience.

[9]  J. Götz,et al.  Profiling Murine Tau with 0N, 1N and 2N Isoform-Specific Antibodies in Brain and Peripheral Organs Reveals Distinct Subcellular Localization, with the 1N Isoform Being Enriched in the Nucleus , 2013, PloS one.

[10]  L. Ittner,et al.  ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke , 2013, Journal of neural transmission.

[11]  Meaghan Morris,et al.  Age-appropriate cognition and subtle dopamine-independent motor deficits in aged Tau knockout mice , 2013, Neurobiology of Aging.

[12]  G. Kempermann,et al.  An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis , 2013, Front. Neurosci..

[13]  Blaine R. Roberts,et al.  Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export , 2012, Nature Medicine.

[14]  D. Wilcock,et al.  Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease , 2010, Neuroscience.

[15]  Jürgen Götz,et al.  Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models , 2010, Cell.

[16]  G. Schellenberg,et al.  Tau isoform regulation is region‐ and cell‐specific in mouse brain , 2008, The Journal of comparative neurology.

[17]  Jürgen Götz,et al.  Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia , 2008, Proceedings of the National Academy of Sciences.

[18]  J. Trojanowski,et al.  Tau-mediated neurodegeneration in Alzheimer's disease and related disorders , 2007, Nature Reviews Neuroscience.

[19]  L. Mucke,et al.  Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model , 2007, Science.

[20]  L. Ittner,et al.  The N-terminal extracellular domain 23-60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1. , 2005, Biochemistry.

[21]  N. Shahani,et al.  Functions and malfunctions of the tau proteins , 2002, Cellular and Molecular Life Sciences CMLS.

[22]  M. Vitek,et al.  Tau is essential to β-amyloid-induced neurotoxicity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Crabtree,et al.  Bidirectional transcriptional activity of PGK‐neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice , 2001, Genesis.

[24]  M. Vitek,et al.  Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. , 2001, Journal of cell science.

[25]  N. Hirokawa,et al.  Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes , 2000, The Journal of cell biology.

[26]  Patrick R. Hof,et al.  Tau protein isoforms, phosphorylation and role in neurodegenerative disorders 1 1 These authors contributed equally to this work. , 2000, Brain Research Reviews.

[27]  Wen-Lang Lin,et al.  Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein , 2000, Nature Genetics.

[28]  N. Hirokawa,et al.  Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice , 2000, Neuroscience Letters.

[29]  W. Kamphorst,et al.  Phenotypic variation in hereditary frontotemporal dementia with tau mutations , 1999, Annals of neurology.

[30]  T. Ley,et al.  Long-range disruption of gene expression by a selectable marker cassette. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  N. Hirokawa,et al.  Altered microtubule organization in small-calibre axons of mice lacking tau protein , 1994, Nature.

[32]  N. Cairns,et al.  Tau proteins of alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms , 1992, Neuron.

[33]  Y. Barde,et al.  Neurotrophins are required for nerve growth during development , 2001, Nature Neuroscience.