GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of GABRA2 brain protein and mRNA in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair deletion located in an intron adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR--mediated gene editing on a B6J genetic background completely restored brain levels of GABRA2 protein and mRNA. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the gene is of critical importance to molecular genetic studies in neurobiological research because this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by GABRA2 function.
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http://dx.doi.org/10.3389/fgene.2019.00188 | DOI Listing |
Aging is a complex biological process. Several animal models, including nematodes, Drosophila, and rodents, have been used in research on aging mechanisms and the extension of healthy life expectancy. The present study investigated the physiological and anatomical changes associated with aging in two sub-strains of aged C57BL/6 mice used in aging research: C57Bl/6NCrSlc (B6N) and C57BL/6J (B6J).
View Article and Find Full Text PDFNeuropsychopharmacol Rep
March 2025
Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Japan.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T Itpr3/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood.
View Article and Find Full Text PDFbioRxiv
October 2024
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609.
Frailty indexes (FIs) capture health status in humans and model organisms. To accelerate our understanding of biological aging and carry out scalable interventional studies, high-throughput approaches are necessary. We previously introduced a machine vision-based visual frailty index (vFI) that uses mouse behavior in the open field to assess frailty using C57BL/6J (B6J) data.
View Article and Find Full Text PDFNutrients
September 2024
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
The objective of this study was to determine the influence of sex and strain on striatal and nucleus accumbens dopamine neurochemistry and dopamine-related behavior due to a high-saturated-fat diet (HFD). Male and female C57B6/J (B6J) and Balb/cJ (Balb/c) mice were randomly assigned to a control-fat diet (CFD) containing 10% kcal fat/g or a mineral-matched HFD containing 60% kcal fat/g for 12 weeks. Intraperitoneal glucose tolerance testing (IPGTT) and elevated plus maze experiments (EPM) confirmed that an HFD produced marked blunting of glucose clearance and increased anxiety-like behavior, respectively, in male and female B6J mice.
View Article and Find Full Text PDFInt J Cardiol
December 2024
Department of General Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address:
Background: Atrial fibrosis is associated with the pathogenesis of atrial fibrillation (AF). This study aims to discuss the function of circ_0079480 in atrial fibrosis and its underlying mechanism.
Methods: In vitro and in vivo models of atrial fibrosis were established by using angiotensin II (Ang II) to treat human atrial fibroblasts (HAFs) and C57/B6J mice.
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