Dysdifferentiative Nature of Aging: Age-Dependent Expression of MuLV and Globin Genes in Thymus, Liver and Brain in the AKR Mouse Strain

Ono, Tetsuya; Dean, Roger G.; Chattopadhyay, Sisir K.; Cutler, Richard G.

doi:10.1159/000212725

Cited by 24 publications

(12 citation statements)

References 25 publications

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“…Profiles for the AKR/J strain include high rates of leukemia, which leads to a shortened lifespan [e.g. 90]. Early mortality in the AKR/J group of the present study necessitated conducting the water maze test earlier in the testing sequence, using a second set of mice.…”

Section: Discussionmentioning

confidence: 99%

“…While the group remained healthy throughout the T-maze testing, eleven of the mice died or were euthanized due to weight loss before the start of the water maze testing, possibly due to the high rate of leukemia reported for this strain (e.g. 90). A separate group of 20 AKR/J mice were tested, using the sequence described above, but with water maze testing conducted at an earlier time point (age 3-4 months), rather than the T-maze test.…”

Section: Test Proceduresmentioning

confidence: 99%

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Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains

Moy¹,

Nadler²,

Young³

et al. 2007

Behavioural Brain Research

717

795

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Three defining clinical symptoms of autism are aberrant reciprocal social interactions, deficits in social communication, and repetitive behaviors, including motor stereotypies and insistence on sameness. We developed a set of behavioral tasks designed to model components of these core symptoms in mice. Male mice from ten inbred strains were characterized in assays for sociability, preference for social novelty, and reversal of the spatial location of the reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J, DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability, while A/J, BALB/cByJ, BTBR T + tf/J, and 129S1/SvImJ mice did not. C57BL/6J, C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T + tf/J showed significant preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did not. Normal scores on relevant control measures confirmed general health and physical abilities in all strains, ruling out artifactual explanations for social deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J, BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social approach. Strains that showed high levels of performance on acquisition of a Tmaze task were also able to reach criterion for reversal learning. On the Morris water maze task, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DBA/2J, AKR/J, BTBR T + tf/J, and 129S1/SvImJ failed to show significant quadrant preference during the reversal probe trial. These results highlight a dissociation between social task performance and reversal learning. BTBR T + tf/J is a particularly interesting strain, displaying both low social approach and resistance to change in routine on the water maze, consistent with an autism-like phenotype. Our multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

Section: Test Proceduresmentioning

confidence: 99%

Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains

Moy¹,

Nadler²,

Young³

et al. 2007

Behavioural Brain Research

717

795

View full text Add to dashboard Cite

show abstract

“…Indeed, there appears to be a general correlation between ageing and progressive demethylation of the RTNs [50,51]. Three studies have reported activation of specific, individual RTNs during ageing [52][53][54], one of these [52] involving the activation of a lymphoma-associated HERV.…”

Section: A S Wilkinsmentioning

confidence: 99%

The enemy within: An epigenetic role of retrotransposons in cancer initiation

Wilkins

2010

BioEssays

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This article proposes that cancers can be initiated by retrotransposon (RTN) activation through changes in the transcriptional regulation of nearby genes. I first detail the hypothesis and then discuss the nature of physiological stress(es) in RTN activation; the role of DNA demethylation in the initiation and propagation of new RTN states; the connection between ageing and cancer incidence and the involvement of activated RTNs in the chromosomal aberrations that feature in cancer progression. The hypothesis neither replaces nor invalidates other theories of cancer, in particular the somatic mutation theory, but helps clarify and unify much of the hitherto poorly integrated, complex phenomenology of cancer.

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“…These programmed events include, for example, the changes in gene expression associated with the loss of hormonal balance (32,34). We are directing our efforts toward an understanding of the programmed changes in gene expression and metabolism that are normally associated with the process of aging.It has been observed for some time that aging is accompanied by an overall deregulation of gene activity (10,29,30,45). At the same time, several investigators have reported changes in the transcriptional activity of specific genes in several organisms (14,34,35,41,46,47).…”

mentioning

confidence: 99%

“…It has been observed for some time that aging is accompanied by an overall deregulation of gene activity (10,29,30,45). At the same time, several investigators have reported changes in the transcriptional activity of specific genes in several organisms (14,34,35,41,46,47).…”

mentioning

confidence: 99%

T-kininogen gene expression is induced during aging.

Sierra¹,

Fey²,

Guigoz³

1989

Mol. Cell. Biol.

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We have constructed a cDNA library from senescent (24-month-old) rat liver mRNA and, by differential screening, have selected clones corresponding to mRNA species with increased abundance in aging rats. Direct sequencing of the inserts indicated that most of the clones (9 of 10) contained sequences coding for T-kininogen, also called major acute-phase protein, cysteine protease inhibitor, or thiostatin. Nuclear elongation experiments showed that the increase in mRNA concentration was controlled at the transcriptional level. RNase mapping and Si analysis indicated that the age-dependent induction operated preferentially at one of the three transcriptional start sites of the gene(s). The acute-phase reaction (inflammation) is known to also induce these genes at the level of transcription; however, two of the three start sites are induced by inflammation. Transcription from one of these sites was induced by both phenomena, aging and inflammation.During the past few years, major efforts have been made to understand developmental processes at the molecular level. Although many researchers have directed their efforts toward an understanding of the changes in gene expression that accompany early development, surprisingly little is known about the molecular changes that occur as the ultimate result of development, namely, senescence.We are particularly interested in the process of aging as well as the factors that might be able to affect this process. The phenomenon of aging is the result of an interplay of various components, both extrinsic (such as nutritional status or physical exercise) and intrinsic. The intrinsic processes can in turn be subdivided into two distinct classes: random events, which are usually triggered by extrinsic events such as UV irradiation or free-radical formation, and programmed events, which are inherently associated with the developmental pathway of the species in question. These programmed events include, for example, the changes in gene expression associated with the loss of hormonal balance (32,34). We are directing our efforts toward an understanding of the programmed changes in gene expression and metabolism that are normally associated with the process of aging.It has been observed for some time that aging is accompanied by an overall deregulation of gene activity (10,29,30,45). At the same time, several investigators have reported changes in the transcriptional activity of specific genes in several organisms (14,34,35,41,46,47). In many cases, transcriptional activity is reduced during aging because of the dependence of some genes on hormonal control. One such example is the extinction of expression of the a2U-globulin gene in aging animals (34). In this case, it has been shown that the gene is turned off not only because of a diminishing level of several controlling hormones but also because the receptors for these hormones appear to diminish with age (33). In addition, a recent report has shown that in aging animals, the a2U-globulin genes are detached from the nuclear matrix (28)....

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Dysdifferentiative Nature of Aging: Age-Dependent Expression of MuLV and Globin Genes in Thymus, Liver and Brain in the AKR Mouse Strain

Cited by 24 publications

References 25 publications

Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains

Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains

The enemy within: An epigenetic role of retrotransposons in cancer initiation

T-kininogen gene expression is induced during aging.

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