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Lessons from tau-deficient mice.

Ke YD, Suchowerska AK, van der Hoven J, De Silva DM, Wu CW, van Eersel J, Ittner A, Ittner LM - Int J Alzheimers Dis (2012)

Bottom Line: This unifying pathology led to the umbrella term "tauopathies" for these conditions, also emphasizing the central role of tau in AD and FTD.Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease.Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations.

View Article: PubMed Central - PubMed

Affiliation: Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.

ABSTRACT
Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term "tauopathies" for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between Aβ and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo.

No MeSH data available.


Related in: MedlinePlus

Homologous recombination strategies for the generation of different tau knockout mice reported by (a) Harada and collegues [39], (b) Tucker and colleagues [41], (c) Dawson and colleagues [40], and (d) Fujio and colleagues [42].
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fig1: Homologous recombination strategies for the generation of different tau knockout mice reported by (a) Harada and collegues [39], (b) Tucker and colleagues [41], (c) Dawson and colleagues [40], and (d) Fujio and colleagues [42].

Mentions: In 1994, Harada and colleagues reported the first tau knockout mouse line (Figure 1(a)) [39]. The mice are viable and macroscopically normal. While immunohistochemical analysis did not show changes, electron microscopical analysis revealed decreased microtubule density in axons, together with reduced cross-bridging between parallel microtubules, and between microtubules and the plasma membrane. Interestingly, neurons from this particular strain showed normal axonal development in culture [39, 45]. The lack of tau was associated with an up to 2 fold increase in the microtubule-associated protein 1A (MAP1A) expression in 7-day-old, and a 1.3 fold increase in adult tau knockout mice, possibly compensating for the absence of tau [39]. Although MAP1B levels were reportedly normal in this tau knockout line, cross-breeding of tau with MAP1B knockout mice exacerbated hypoplastic axon tracts, disorganized neuronal layering, and impaired maturation of primary neurons of MAP1B mice [45].


Lessons from tau-deficient mice.

Ke YD, Suchowerska AK, van der Hoven J, De Silva DM, Wu CW, van Eersel J, Ittner A, Ittner LM - Int J Alzheimers Dis (2012)

Homologous recombination strategies for the generation of different tau knockout mice reported by (a) Harada and collegues [39], (b) Tucker and colleagues [41], (c) Dawson and colleagues [40], and (d) Fujio and colleagues [42].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375147&req=5

fig1: Homologous recombination strategies for the generation of different tau knockout mice reported by (a) Harada and collegues [39], (b) Tucker and colleagues [41], (c) Dawson and colleagues [40], and (d) Fujio and colleagues [42].
Mentions: In 1994, Harada and colleagues reported the first tau knockout mouse line (Figure 1(a)) [39]. The mice are viable and macroscopically normal. While immunohistochemical analysis did not show changes, electron microscopical analysis revealed decreased microtubule density in axons, together with reduced cross-bridging between parallel microtubules, and between microtubules and the plasma membrane. Interestingly, neurons from this particular strain showed normal axonal development in culture [39, 45]. The lack of tau was associated with an up to 2 fold increase in the microtubule-associated protein 1A (MAP1A) expression in 7-day-old, and a 1.3 fold increase in adult tau knockout mice, possibly compensating for the absence of tau [39]. Although MAP1B levels were reportedly normal in this tau knockout line, cross-breeding of tau with MAP1B knockout mice exacerbated hypoplastic axon tracts, disorganized neuronal layering, and impaired maturation of primary neurons of MAP1B mice [45].

Bottom Line: This unifying pathology led to the umbrella term "tauopathies" for these conditions, also emphasizing the central role of tau in AD and FTD.Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease.Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations.

View Article: PubMed Central - PubMed

Affiliation: Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.

ABSTRACT
Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term "tauopathies" for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between Aβ and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo.

No MeSH data available.


Related in: MedlinePlus