Thursday, April 25, 2024 4/25/2024

STUDY ON NEURODEGENERATION USING TDP-43 TRANSGENIC RATS

Award Number: R01NS073829
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

¿ DESCRIPTION (provided by applicant): Among known ALS genes, TDP-43 is of particular interest because its protein is hyper-phosphorylated and ubiquitinated in sporadic ALS. Compared with genetic mutation, post-translational modification is difficult to detect in patients and hard to reproduce in animal models. Therefore, a critical step toward understanding TDP-43 pathogenesis is revealing the pathways by which mutant TDP-43 causes neurodegeneration in ALS. TDP-43 binds to many RNAs and proteins, but how pathogenic mutation impacts TDP-43 function has not yet been determined, particularly in an appropriate animal model. Unexpectedly, overexpression of both WT and mutant TDP-43 in rodents causes indistinguishable phenotypes, indicating that excessive TDP-43 is neurotoxic. Because transgene expression is heavily influenced by position effect, the patterns and levels of transgene expression vary greatly from line to line. Whether mutant TDP-43 is more or less toxic than its WT form thus cannot be determined using existing transgenic models. The question regarding the impact of pathogenic mutation on TDP-43 function is further confounded by observations that TDP-43 depletion induces neurodegeneration in TDP-43 knock-out and knock-down mice. As TDP-43 binds to the 3'-untranslated region of its own mRNA and thereby regulates its own expression, the cDNA knock-in (KI) approach destroys TDP-43 self-regulatory machinery, rendering TDP-43 KI animals not very useful. Even 7 years after the discovery of TDP-43 mutation in ALS, whether mutant TDP-43 causes ALS through a gain or loss of function is still uncertain, and this unresolved issue is a roadblock to unraveling TDP-43 disease mechanisms. To resolve this critical issue, we created KI rats by introducing a single disease-linked point mutation into the rat genome. With the unprecedented rat models, we will determine how pathogenic mutation impacts TDP-43 function in a systematic manner.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = -$183 )
2022	2020	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	7/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$183
														Subtotal = -$183

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	5/23/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$20,811
2021	2019	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	5/23/2021	NON-COMPETING CONTINUATION	-$20,811
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $314,775 )
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	8/20/2020	NON-COMPETING CONTINUATION	-$314,775
2020	2020	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	11	8/20/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$314,775
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	2/24/2020	NON-COMPETING CONTINUATION	$314,775
														Subtotal = $314,775

Issue Date FY: 2019 ( Subtotal = $314,775 )
2019	2019	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	12/5/2018	NON-COMPETING CONTINUATION	$314,775
														Subtotal = $314,775

Issue Date FY: 2018 ( Subtotal = $314,775 )
2018	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	6/20/2018	NON-COMPETING CONTINUATION	$31,478
2018	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	11/21/2017	NON-COMPETING CONTINUATION	$283,297
														Subtotal = $314,775

Issue Date FY: 2017 ( Subtotal = $354,104 )
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	6	7/31/2017	NON-COMPETING CONTINUATION	$12,854
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	007	6	7/31/2017	NON-COMPETING CONTINUATION	$12,854
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	4/18/2017	NON-COMPETING CONTINUATION	-$63,507
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	3/7/2017	NON-COMPETING CONTINUATION	-$226,424
2017	2017	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	008	7	9/15/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$34,125
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/1/2016	NON-COMPETING CONTINUATION	$307,125
2017	2017	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	7	4/18/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$63,507
2017	2017	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	3/8/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$226,424
2017	2017	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	7	7/31/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$12,854
														Subtotal = $354,104

Issue Date FY: 2016 ( Subtotal = $341,250 )
2016	2016	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	12/15/2015	COMPETING CONTINUATION	$341,250
2016	2015	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/15/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $341,250

Issue Date FY: 2015 ( Subtotal = $339,063 )
2015	2015	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/4/2014	NON-COMPETING CONTINUATION	$305,156
2015	2015	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/14/2015	NON-COMPETING CONTINUATION	$33,907
														Subtotal = $339,063

Issue Date FY: 2014 ( Subtotal = $335,673 )
2014	2014	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/7/2014	NON-COMPETING CONTINUATION	$30,517
2014	2014	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/25/2013	NON-COMPETING CONTINUATION	$305,156
														Subtotal = $335,673

Issue Date FY: 2013 ( Subtotal = $327,196 )
2013	2013	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	10/29/2012	NON-COMPETING CONTINUATION	$305,156
2013	2013	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/23/2013	NON-COMPETING CONTINUATION	$22,040
														Subtotal = $327,196

Issue Date FY: 2012 ( Subtotal = $324,625 )
2012	2012	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/2/2011	NEW	$324,625
														Subtotal = $324,625

Grand Total All Awards = $2,966,053

Top

All Categories

About

Search

Reports

Data Submission

Award Information

STUDY ON NEURODEGENERATION USING TDP-43 TRANSGENIC RATS

Award Number: R01NS073829

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer