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A Neurobehavioral Endophenotype of t...

Hunsaker, Michael Ryan.

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A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation./
Author:	Hunsaker, Michael Ryan.
Description:	525 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.
Contained By:	Dissertation Abstracts International74-02B(E).
Subject:	Biology, Neuroscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3540517
ISBN:	9781267657015

A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation.
Hunsaker, Michael Ryan.

A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation. - 525 p.

Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.

Thesis (Ph.D.)--University of California, Davis, 2012.

The fragile X premutation is a CGG repeat expansion on the FMR1 gene between 55 and 200 repeats in length. Carriers of the fragile X premutation show a complex phenotype that includes a number of disparate features, including difficulty with mental arithmetic and visuospatial processing. Despite these reports, there is no agreement concerning which behavioral features are central to the fragile X premutation phenotype. The goal of this dissertation was to develop a series of behavioral tasks that, when looked at as a whole, define a pattern of behavioral phenotypes that scale with the dosage of the FMR1 CGG repeat lengths (i.e., genetic dosage).

ISBN: 9781267657015Subjects--Topical Terms:

1017680
Biology, Neuroscience.

A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation.
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020 $a 9781267657015
035 $a (MiAaPQ)AAI3540517
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100 1 $a Hunsaker, Michael Ryan. $3 3168775
245 1 2 $a A Neurobehavioral Endophenotype of the CGG KI Mouse Model of the Fragile X Premutation.
300 $a 525 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.
500 $a Adviser: Paul J. Hagerman.
502 $a Thesis (Ph.D.)--University of California, Davis, 2012.
520 $a The fragile X premutation is a CGG repeat expansion on the FMR1 gene between 55 and 200 repeats in length. Carriers of the fragile X premutation show a complex phenotype that includes a number of disparate features, including difficulty with mental arithmetic and visuospatial processing. Despite these reports, there is no agreement concerning which behavioral features are central to the fragile X premutation phenotype. The goal of this dissertation was to develop a series of behavioral tasks that, when looked at as a whole, define a pattern of behavioral phenotypes that scale with the dosage of the FMR1 CGG repeat lengths (i.e., genetic dosage).
520 $a Neuropathological studies were designed to quantify the pathological features in carriers of the fragile X premutation and fragile X syndrome, and subsequently compare those findings with the mouse model. These experiments revealed the CGG KI mouse model of the fragile X premutation recapitulated the pathological features present in aged premutation carriers. These data suggest the CGG KI mouse model is a valid model to study the development and progression of the neuropathological features associated with the premutation.
520 $a The present behavioral studies characterized effects of the fragile X premutation on cognitive function by examining the performance of CGG KI mice with CGG repeat expansions ranging between 70-200 repeats using behavioral tasks emphasizing spatiotemporal, visuospatial, and visuomotor function. In all cases CGG KI mice showed deficits that worsened as a function of increasing Fmr1 CGG repeat lengths. Furthermore, increasing CGG repeat length resulted in reduced LTP, LTD, and mGluR1/5 LTD during the first 10-20 minutes after conditioning stimuli were applied, but there was no effect for CGG repeat length on plasticity at 40-60 minutes after conditioning stimuli were applied.
520 $a These results provide evidence for a complex neurocognitive endophenotype in the CGG KI mouse model. Importantly, the deficits observed for the CGG KI mice on the behavioral tasks and measures of plasticity scale with increasing genetic dosage (i.e., increasing CGG repeat length), supporting reports in human carriers of the fragile X premutation that suggest increasing CGG repeat length modulates cognitive function.
590 $a School code: 0029.
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Psychology, Psychobiology. $3 1017821
650 4 $a Psychology, Behavioral Sciences. $3 1669657
690 $a 0317
690 $a 0349
690 $a 0602
710 2 $a University of California, Davis. $b Neuroscience. $3 3168776
773 0 $t Dissertation Abstracts International $g 74-02B(E).
790 $a 0029
791 $a Ph.D.
792 $a 2012
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3540517