A wide variety of CreER driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreER driver line targeted to the endogenous mouse doublecortin locus as a marker of fate-specified neuroblasts and immature neurons. Our new model places a T2A-CreER cassette immediately downstream of the Dcx coding sequence on the X chromosome, allowing expression of both Dcx and CreER proteins in the endogenous spatiotemporal pattern for this gene. We demonstrate that the new mouse line drives expression of a Cre-dependent reporter throughout the brain in neonatal mice and in known neurogenic niches of adult animals. The line has been deposited with the Jackson Laboratory and should provide an accessible tool for studies targeting fate-restricted neuronal precursors.
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http://dx.doi.org/10.1002/dvg.23584 | DOI Listing |
Microb Cell Fact
January 2025
MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China.
Background: Hyaluronic acid (HA) is extensively employed in various fields such as medicine, cosmetics, food, etc. The molecular weight (MW) of HA is crucial for its biological functions. Streptococcus zooepidemicus, a prominent HA industrial producer, naturally synthetizes HA with high MW.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Bacterial artificial chromosome transgenic models, including most Cre-recombinases, enable potent interrogation of gene function in vivo but require rigorous validation as limitations emerge. Due to its high relevance to metabolic studies, we perform comprehensive analysis of the Ucp1-Cre line which is widely used for brown fat research. Hemizygotes exhibit major brown and white fat transcriptomic dysregulation, indicating potential altered tissue function.
View Article and Find Full Text PDFJ Neurosci
January 2025
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA
The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Sonata Therapeutics Inc, Watertown, Massachusetts, USA
Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.
View Article and Find Full Text PDFNeurosci Res
January 2025
RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address:
In mammals, lactation is essential for the health and growth of infants and supports the formation of the mother-infant bond. Breastfeeding is mediated by the neurohormone oxytocin (OT), which is released into the bloodstream in a pulsatile manner from OT neurons in the hypothalamus to promote milk ejection into mammary ducts. While classical studies using anesthetized rats have illuminated the activity patterns of putative OT neurons during breastfeeding, the molecular, cellular, and neural circuit mechanisms driving the synchronous pulsatile bursts of OT neurons in response to nipple stimulation remain largely elusive.
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