View Project Donarum-3R01NS040270-03S1

Project Summary
Status:	Public
Publications:	2 Published
Project Detail		Data Detail
Platform:	Affymetrix	MIAME Areas	Compliance
Species:	Mouse	Array Design Detail	true
Organ/Tissue Type:	brain	Experiment Detail	false
Organ Region:	hippocampus	Sample Detail	false
Cell Type:	HEK293 cells and CB1HEK293 cells	Hybridization Detail	false
Study Type:	subclassification	Measurement Detail	false
Disease/Condition:	21q monosomy
Replicates:	0
Expected Samples:	18

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Investigator Contact Detail
Name	Elizabeth A Donarum
Institution:	Barrow Neurological Institute
Street Address:	NRC 438, Barrow Neurological Institute, St Joseph's Hospital and Medical Center
	350 West Thomas Road
City, State/Province:	Phoenix , AZ
Zip/Postal Code:	85013
Country:	United States
Work Phone:	602-406-3130
Fax:	602-406-7172
E-mail:	LDonarum@chw.edu

Proposal Detail

Grant:

3R01NS040270-03S1

Status:

Public

Service Type:

Start to Finish Profiling

IACUC:

A773

IACUC date:

2000-01-01

Study Relevance:

Succinate semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder effecting approximately 350 people around the world. Patients suffering from SSADH deficiency experience language acquisition failure, memory deficiencies, autism, increased aggressive behaviors, and seizures. There is a chemical buildup of both gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) in the neurological system of these patients. The Aldh5a1-/- knock out mouse model of SSADH deficiency shows the same chemical imbalances as the human disease, with additional fatal tonic-clonic seizures at three weeks of age. The elucidation of seizure causing pathways will facilitate treatment of seizure phenotypes in diseases with related epilepsy.

Hypothesis:

We hypothesis that the SSADH deficient mice experience a dysfunction of glutamate/GABA/ glutamine neurotransmitter cycle linked to astroglial metabolism and/or uptake of neuronally-released glutamate. The increased levels of GHB and GABA lead to down regulation of GABA-B-Receptor leading to seizures. The SSADH deficient phenotype may also be caused by ongoing oxidative damage and the pathological role of succinic semialdehyde.

Specific Aim:

Gene expression patterns within the hippocampus, cerebellum, and cortex of SSADH deficient mice (Aldh5a1-/- mice) will be compared to wild type mice at a time point immediately prior to fatal seizures.

Experimental Procedure and Design:

SSADH deficient mice (Aldh5a1-/- knock out) exhibit fatal seizures around three weeks of age. Mutant and wild type mice will be sacrificed between 17 and 19 days of life, and brain sections will be extracted and frozen (using a standard protocol). Hippocampus, cerebellum, and cortex from three mutant mice and three wild type mice will individually be expression profiled on the Affymetrix platform, giving a total of eighteen arrays. Comparative analysis will then be carried out, evaluating the transcript differences between mutant and wild type mice in each brain region.

Experimental Factors:

Conditions that are tested in the experiment. At least one is required. Experimental factors are the independent variables in the experiment.


Experimental Factors is empty.

Project Samples

Samples associated with this project.

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Name	Description	Bio-Source	Extracts
Aldh5a1-/- #3363 Hippo	Hippocampus	BioSource18	1
Aldh5a1-/- #3363 Cereb	Cerebellum	BioSource19	1
Aldh5a1-/- #3363 Cort	Cortex	BioSource20	1
Aldh5a1-/- #3389 Hippo	Hippocampus	BioSource21	1
Aldh5a1-/- #3389 Cereb	Cerebellum	BioSource22	1
Aldh5a1-/- #3389 Cort	Cortex	BioSource23	1
Aldh5a1-/- #3403 Hippo	Hippocampus	BioSource24	1
Aldh5a1-/- #3403 Cereb	Cerebellum	BioSource25	1
Aldh5a1-/- #3403 Cort	Cortex	BioSource26	1
Wt #3405 Hippo	Hippocampus	BioSource27	1
Wt #3405 Cereb	Cerebellum	BioSource28	1
Wt #3405 Cort	Cortex	BioSource29	1
Wt #3406 Hippo	Hippocampus	BioSource30	1
Wt #3406 Cereb	Cerebellum	BioSource31	1
Wt #3406 Cort	Cortex	BioSource32	1
Wt #3396 Hippo	Hippocampus	BioSource33	1
Wt #3396 Cereb	Cerebellum	BioSource34	1
Wt #3396 Cort	Cortex	BioSource35	1

Project Hybridizations

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