Article
Multidisciplinary Sciences
Lilach Simchi, Hanoch Kaphzan
Summary: This study examined affiliative and aggressive social behavior in AS mice, finding unique characteristics in social stimulus habituation and significantly enhanced aggression compared to their WT littermates. The findings highlight the use of AS mouse model for characterizing and measuring inappropriate aggressive behavior, suggesting potential therapeutic interventions.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Nikhil J. Pandya, Sonja Meier, Stefka Tyanova, Marco Terrigno, Congwei Wang, A. Mattijs Punt, E. J. Mientjes, Audrey Vautheny, Ben Distel, Thomas Kremer, Ype Elgersma, Ravi Jagasia
Summary: This study investigates the mechanisms and potential therapeutic options for Angelman syndrome. Proteomics analysis reveals changes in protein pathways during different stages of development in an AS mouse model. Restoring UBE3A expression is shown to reverse these changes and provide a promising treatment option. Additionally, a novel UBE3A substrate is discovered, and a protein database is created to support future research.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Laure Lecoin, Bowen Dempsey, Alexandra Garancher, Steeve Bourane, Pierre-Louis Ruffault, Marie-Pierre Morin-Surun, Nathalie Rocques, Martyn Goulding, Alain Eychene, Celio Pouponnot, Gilles Fortin, Jean Champagnat
Summary: Apneas are associated with various pathological and fatal conditions. This study shows that a mutation in the transcription factor Mafa leads to an abnormally high incidence of breath holding apneas and death in newborn mice. The mutation affects GABAergic inhibitory neurons, causing decreased motor drive to muscles controlling the airways.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Kara A. Lau, Xin Yang, Mengia S. Rioult-Pedotti, Stephen Tang, Mark Appleman, Jianan Zhang, Yuyang Tian, Caitlin Marino, Mudi Yao, Qin Jiang, Ayumi C. Tsuda, Yu-Wen Alvin Huang, Cong Cao, John Marshall
Summary: Angelman Syndrome (AS) is a severe cognitive disorder caused by loss of neuronal expression of the E3 ubiquitin ligase UBE3A. Researchers have found that a peptidomimetic compound called CN2097, which binds to the TrkB-associated scaffolding protein PSD-95, can restore synaptic plasticity and learning deficits in AS mice. CN2097 normalizes autophagy and restores synaptic protein levels, leading to improvements in cognitive and motor function.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Cell Biology
Lei Xing, Jeremy M. Simon, Travis S. Ptacek, Jason J. Yi, Lipin Loo, Hanqian Mao, Justin M. Wolter, Eric S. McCoy, Smita R. Paranjape, Bonnie Taylor-Blake, Mark J. Zylka
Summary: The Ube3a gene mutation can cause neurodevelopmental disorders regardless of parent of origin. A mouse model with the autism-linked UBE3AT485A gain-of-function mutation was created. Both paternal and maternal expression of UBE3AT503A led to increased UBE3A activity in neural progenitors and glial cells. Maternal expression of UBE3AT503A also resulted in elevated UBE3A activity in neurons, but not paternal expression. The phenotypes of mutant mice differed depending on the parent of origin.
Article
Cell Biology
Linn Amanda Syding, Agnieszka Kubik-Zahorodna, Petr Nickl, Vendula Novosadova, Jana Kopkanova, Petr Kasparek, Jan Prochazka, Radislav Sedlacek
Summary: A novel mouse model with a complete deletion of the Ube3a gene exhibits important phenotypes characteristic of Angelman syndrome, including motor dysfunction and behavioral abnormalities.
Article
Cell Biology
Mary Jo Talley, Diana Nardini, Nisha Shabbir, Lisa A. Ehrman, Carlos E. Prada, Ronald R. Waclaw
Summary: The study reveals the expression and function of Lztr1 in different regions of the developing brain, particularly its role in oligodendrocyte and astrocyte development. The results provide insights into the impact of Lztr1 deficiency on brain development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Luisa Di Menna, Rosamaria Orlando, Giovanna 'Errico, Roxana Paula Ginerete, Agata Machaczka, Carmela Maria Bonaccorso, Andrea Arena, Michela Spatuzza, Roberta Celli, Marika Alborghetti, Eleonora Ciocca, Anna Rita Zuena, Mariarosaria Scioli, Valeria Bruno, Giuseppe Battaglia, Ferdinando Nicoletti, Maria Vincenza Catania
Summary: The involvement of mGlu5 receptors in monogenic autism has been supported by various studies, but there is a lack of research on the canonical signal transduction pathway activated by these receptors in mouse models of autism. In this study, we developed a method to assess PI hydrolysis in vivo and found that mGlu5 receptor-mediated PI hydrolysis was impaired in different brain regions of mice modeling Angelman syndrome and fragile-X syndrome. These findings provide the first evidence that the canonical transduction pathway of mGlu5 receptors is downregulated in mouse models of monogenic autism.
Article
Medicine, General & Internal
David E. Godler, Ling Ling, Dinusha Gamage, Emma K. Baker, Minh Bui, Michael J. Field, Carolyn Rogers, Merlin G. Butler, Alessandra Murgia, Emanuela Leonardi, Roberta Polli, Charles E. Schwartz, Cindy D. Skinner, Angelica M. Alliende, Lorena Santa Maria, James Pitt, Ronda Greaves, David Francis, Ralph Oertel, Min Wang, Cas Simons, David J. Amor
Summary: The findings of this study suggest that screening for all chromosome 15 imprinting disorders using SNRPN methylation analysis is feasible, with 5 individuals identified out of 16,579 infants screened.
Article
Neurosciences
Prudhvi Raj Rayi, Hanoch Kaphzan
Summary: Angelman syndrome is a neurogenetic disorder characterized by developmental delay, speech impairment, and other symptoms. Studies have shown that hippocampal deficits in AS mice may be related to altered calcium dynamics and increased alpha 1-Na/K-ATPase expression levels. However, the causal link between hippocampal deficits and major behavioral phenotypes in AS is still unclear.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Yixiong Wang, Lubna Yasmin, Lei Li, Pinzhang Gao, Xia Xu, Xuejun Sun, Roseline Godbout
Summary: Researchers have discovered that the DEAD box protein DDX1 forms large aggregates in the cytoplasm of early mouse embryos and is involved in the formation of Membrane Associated RNA-containing Vesicles. Loss of Ddx1 leads to embryonic lethality and affects mitochondria function, as well as the spatial distribution of calcium in embryos. Furthermore, DDX1 plays a crucial role in regulating developmental and mitochondrial processes in embryos.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Julia Panov, Hanoch Kaphzan
Summary: The study identified dysregulated calcium-related genes in the hippocampus of AS mouse models, which were also found in other human cellular models, strengthening the findings. The compromised calcium signaling in Angelman syndrome may have significant downstream implications and implications for other neurodevelopmental disorders.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Multidisciplinary Sciences
Monica Tramullas, James M. Collins, Patrick Fitzgerald, Timothy G. Dinan, Siobhain M. O' Mahony, John F. Cryan
Summary: Through studying female mice, it was found that visceral hypersensitivity is closely related to sex hormones and gut microbiota; germ-free mice showed similar visceral pain responses to colorectal distension as conventional mice, with sensitivity not dependent on estrous cycle stage; ovariectomy induced hypersensitivity only in conventional mice, leading to weight gain.
Article
Reproductive Biology
Noha A. M. Shendy, Amber L. Broadhurst, Kristin Shoemaker, Robert Read, Amy N. Abell
Summary: The kinase activity encoded by the Map3k4 gene is essential for male gonadal sex determination, as its inactivation can lead to embryonic male gonadal sex reversal.
BIOLOGY OF REPRODUCTION
(2021)
Article
Multidisciplinary Sciences
Yuan Pan, Jared D. Hysinger, Tara Barron, Nicki F. Schindler, Olivia Cobb, Xiaofan Guo, Belgin Yalcin, Corina Anastasaki, Sara B. Mulinyawe, Anitha Ponnuswami, Suzanne Scheaffer, Yu Ma, Kun-Che Chang, Xin Xia, Joseph A. Toonen, James J. Lennon, Erin M. Gibson, John R. Huguenard, Linda M. Liau, Jeffrey L. Goldberg, Michelle Monje, David H. Gutmann
Summary: Neurons play an essential role in promoting the growth of certain types of brain tumors, such as optic pathway gliomas driven by mutations in the NF1 tumor suppressor gene. Inhibition of neuronal activity through light deprivation can prevent tumor formation and progression, highlighting a potential therapeutic strategy and the importance of Nf1 mutation-mediated dysregulation of neuronal signaling pathways in cancer predisposition syndromes.