Thursday, July 17, 2025 7/17/2025

Humanized LMNA Animal Model for Detecting Pathogenicity in Clinical Variants

Award Number: R43GM133229
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2021

Group Awards By:

View Award Description

Humanized LMNA Animal Model for Detecting Pathogenicity in Clinical Variants - SUMMARY: The goal of this R43 SBIR grant application is to understand the role of genetic variation in LMNA. For clinicians, the functional significance of 39.6% of the variations in LMNA have the status of being either unknown or a Variants of Uncertain Significance (VUS). As genomic sequencing continues its expanded utilization into the clinic, diagnostic rates will improves as variant function becomes better assigned to either pathogenic or benign status. Animal models have consistently been used as a proxy to understanding variant function. This proposal uses expression of a LMNA cDNA as a gene substitution of the orthologous gene of C. elegans animal model. With 79% of human genes having an identifiable homology in C. elegans, the extension of this humanization process to thousands of genes is possible. This proposal has three specific aims. The first aim is find a recoded version of the human LMNA cDNA that can be insert as a replacement of the orthologous C. elegans lmn1 gene and exhibit a capacity to rescue the function absent in the null allele. In the second aim, known pathogenic and benign variants are installed in the humanized locus and activity defects of the installed variants are measured. In the third aim, variants of uncertain significance and unknown status are installed in the humanized locus and measured for deviance of activity. In future Phase II work, once variant functional behavior is measured, drug activity can be explored for capacity to reverse phenotypes back to wildtype behavior.


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: 2021 ( Subtotal = $0 )
2021	2019	NEMAMETRIX, INC	1505 WESTEC DR	EUGENE	OR	97402	LANE	USA	Biomedical Research and Research Training	000	1	9/4/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $225,000 )
2019	2019	NEMAMETRIX, INC	44 W 7TH AVE	EUGENE	OR	97401	LANE	USA	Biomedical Research and Research Training	000	1	3/26/2019	NEW	$225,000
														Subtotal = $225,000

Grand Total All Awards = $225,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Humanized LMNA Animal Model for Detecting Pathogenicity in Clinical Variants

Award Number: R43GM133229

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2021

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer