We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Gene Editing Prevents Mice from Developing Hereditary Obesity

By LabMedica International staff writers
Posted on 27 Dec 2018
Print article
Image: A molecular model of the Melanocortin 4 receptor (Mc4r) protein (Photo courtesy of Wikimedia Commons).
Image: A molecular model of the Melanocortin 4 receptor (Mc4r) protein (Photo courtesy of Wikimedia Commons).
A modified version of the CRISPR/Cas9 genome-editing tool was used to correct a mutated gene in mice, which prevented the animals from becoming obese.

A wide-range of human diseases results from haploinsufficiency, where the function of one of the two gene copies is lost. One of these diseases can be conveniently studied in a mouse obesity model where mutations in a single copy of the SIM1 (Single-minded homolog 1) or MC4R (Melanocortin 4 receptor) genes cause hereditary obesity.

Investigators at the University of California, San Francisco (USA) targeted the remaining functional copy of a haploinsufficient gene using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype.

CRISPR activation (CRISPRa) is one type of CRISPR tool that use modified versions of dCas9, a mutation of Cas9 without endonuclease activity, with added transcriptional activators on dCas9 or the guide RNAs (gRNAs). Like a standard CRISPR-Cas9 system, dCas9 activation systems rely on similar components such as Cas9 variants for modulation or modification of genes, gRNAs to guide Cas9 to intended targets, and vectors for introduction into cells. However, while a standard CRISPR-Cas9 system relies on creating breaks in DNA through the endonuclease activity of Cas9 and then manipulating DNA repair mechanisms for gene editing, dCas9 activation systems are modified and employ transcriptional activators to increase expression of genes of interest.

The investigators reported in the December 13, 2018, online edition of the journal Science that to evaluate the therapeutic potential of CRISPRa, they had injected an adeno-associated virus vector containing CRISPRa into the hypothalamus, which led to reversal of the obesity phenotype in Sim1 and Mc4r haploinsufficient mice.

Animals that were missing one copy of the SIM1 gene received the CRISPRa injections at four weeks of age and thereafter maintained a healthy body weight. Mice that did not receive CRISPRa started gaining weight at six weeks of age and, by the time they were 10-weeks old, were severely obese. Ultimately, the CRISPRa-treated mice averaged 30 to 40% lighter than their untreated counterparts.

"We thought that if we could increase the dosage of the existing functional copy of the gene, we could prevent many human diseases in individuals harboring these mutations," said senior author Dr. Nadav Ahituv, professor of bioengineering and therapeutic sciences at the University of California, San Francisco.

Related Links:
University of California, San Francisco

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
HLX
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
Cancer Mutation Profiling Liquid Kit
OncoScreen Plus

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.