C11680: Transgenic Mouse Line with Mutated Rent1/UFP1 GeneNovelty:
A transgenic mouse strain with deactivated Nonsense-Mediated Decay (NMD) pathway by the expression of mutated Regulator of Nonsense Transcript (Rent1)/UFP1 protein.
Value Proposition:
The wild-type protein Rent1/UFP1 acts as a trans-effector of the cellular surveillance mechanism called the NMD, which is responsible for eliminating faulty mRNA transcripts before deleterious effects. Therefore, studying the effect of a mutation that deactivates the NMD pathway can open new ways to prevent the condition. This invention comprises of a transgenic mouse line with deactivated NMD pathway through the expression of the mutated Rent1/UFP1 protein. Additional advantages include:
• Immunological studies requiring partial attenuation of T-cell mediated immune response
• Role of genetic disorders in the maturation and activation of the thymus glands
• Can be used for epigenetic studies
• Candidate therapeutic agent screening and characterization
Technical Details:
Johns Hopkins researchers have created a transgenic mouse line (B6.Cg-Tg(ACTB-UFP1*R844C)581Hed/J) that expresses a dominant-negative form of human Rent1 protein encoded by the UFP1 gene. The transgene contains a single amino acid mutation in the position R844C in the highly conserved helicase domain of the Rent1/UFP1 protein. The mutated transgenic model is devoid of the cellular NMD activity and exhibits developmental crisis during the onset of the T-cell receptor (TCR) allele rearrangement. This manifests in poor growth of the thymus, reduced thymocyte populations and a drastic reduction of double positive thymocytes with a corresponding increase of CD25 carrying double negative cells.
Looking for Partners:
To license the technology as a research tool to study developmental disorders of the immune system.
Stage of Development:
Ready for commercial use
Data Availability:
Under CDA / NDA
Publications/Associated Cases:
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10638-43
