Project description:Gene expression profiling of mouse cerebellum in which the experimental strain conditionally lack the Smarca5 gene that encodes for the catalytic subunit of multiple chromatin remodeling complexes. Deletion of Smarca5 was restricted to those cells expressing Cre-recombinase driven by the Nestin promoter. Comparison of gene expression in P0 cerebella of Smarca5 cKO mice versus wild type controls. Three samples of each strain were used in a total of 4 replicates.
Project description:Gene expression profiling of mouse cerebellum in which the experimental strain conditionally lack the Smarca5 gene that encodes for the catalytic subunit of multiple chromatin remodeling complexes. Deletion of Smarca5 was restricted to those cells expressing Cre-recombinase driven by the Nestin promoter. Comparison of gene expression in P10 cerebella of Smarca5 cKO mice versus wild type controls. Three samples of each strain were used in a total of 3 replicates.
Project description:Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), ADHD, learning difficulties and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional Astn2 knockout (KO and cKO, respectively) mouse lines. Astn2 KO mice exhibited strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity, and repetitive behaviors, altered behavior in the three-chamber test, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors were also prominent in Astn2 cKO animals but they did not show altered behavior in the three-chamber test. By Golgi staining, Astn2 KO PCs had region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of Astn2 KO cerebellum revealed a marked upregulation of ASTN2 family member, ASTN1, a neuron-glial adhesion protein. Immunohistochemistry and electron microscopy demonstrated a significant increase in Bergmann glia volume in the molecular layer of Astn2 KO animals. Electrophysiological experiments indicated a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents (IPSCs) in the Astn2 KO animals, suggesting that pre- and postsynaptic components of synaptic transmission were altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.
Project description:Here we utilized a conditional knock-out mouse model to investigate the role of Smarca5, an ISWI subfamily chromatin remodeling ATPase, during thymocyte development using hCD2-iCre transgene. We did transcriptional profiling of FACS-sorted CD4/CD8 double-positive thymocytes as this thymic population was persistent yet strongly underrepresented in adult 6-week mutant thymi. Controls included age-matched CD4/CD8 double-positive thymocytes from wild-type and tumor suppressor protein Trp53-null mice. For comparison, the Smarca5/Trp53-double-deficient thymocytes included in the experiment were partially rescued upon loss of Trp53.
Project description:Tamoxifen-inducible conditional knockout (CKO) mice were generated to explore the function of Gcn1 in adult mice using the Cre/loxP system. To analyze the function of GCN1 in the liver, we compared the whole cell proteome of livers harvested from GCN1 CKO mice with that of wild-type mice.
Project description:Tamoxifen-inducible conditional knockout (CKO) mice were generated to explore the function of Gcn1 in adult mice using the Cre/loxP system. To analyze the function of GCN1 in the intestinal epithelium, we compared the whole cell proteome of jejunum harvested from GCN1 CKO mice with that of wild-type mice.
Project description:Tamoxifen-inducible conditional knockout (CKO) mice were generated to explore the function of Gcn1 in adult mice using the Cre/loxP system. To analyze the function of GCN1 in the intestinal epithelium, we compared the whole cell proteome of duodenum harvested from GCN1 CKO mice with that of wild-type mice.
Project description:Tamoxifen-inducible conditional knockout (CKO) mice were generated to explore the function of Gcn1 in adult mice using the Cre/loxP system. To analyze the function of GCN1 in the intestinal epithelium, we compared the whole cell proteome of ileum harvested from GCN1 CKO mice with that of wild-type mice.