The Experts below are selected from a list of 1779 Experts worldwide ranked by ideXlab platform

Mattei D. - One of the best experts on this subject based on the ideXlab platform.

  • A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions
    'Proceedings of the National Academy of Sciences', 2021
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Pitsch J., Tsortouktzidis D., Velasquez L.m., Voigt A., Schilling K., Mattei D.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available. Therefore, we used CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, Pigv:c.1022C > A (p.A341E), at a site that is conserved in mice. Mirroring the human pathology, mutant Pigv(341E) mice exhibited deficits in motor coordination, cognitive impairments, and alterations in sociability and sleep patterns, as well as increased seizure susceptibility. Furthermore, immunohistochemistry revealed reduced synaptophysin immunoreactivity in Pigv(341E) mice, and electrophysiology recordings showed decreased hippocampal synaptic transmission that could underlie impaired memory formation. In single-cell RNA sequencing, Pigv(341E)-hippocampal cells exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction in Abl1 transcript levels in several cell clusters suggested a link to the signaling pathway of GPI-anchored ephrins. We also observed elevated levels of Hdc transcripts, which might affect Histamine Metabolism with consequences for circadian rhythm. This mouse model will not only open the doors to further investigation into the pathophysiology of GPIBD, but will also deepen our understanding of the role of GPI-anchor–related pathways in brain development

  • A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions
    'Cold Spring Harbor Laboratory', 2020
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Voigt A., Mattei D., Knaus A., Moreno Velasquez L., Long M., Vogt G.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect Histamine Metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

Rodríguez De Los Santos, M. - One of the best experts on this subject based on the ideXlab platform.

  • A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions
    'Proceedings of the National Academy of Sciences', 2021
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Pitsch J., Tsortouktzidis D., Velasquez L.m., Voigt A., Schilling K., Mattei D.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available. Therefore, we used CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, Pigv:c.1022C > A (p.A341E), at a site that is conserved in mice. Mirroring the human pathology, mutant Pigv(341E) mice exhibited deficits in motor coordination, cognitive impairments, and alterations in sociability and sleep patterns, as well as increased seizure susceptibility. Furthermore, immunohistochemistry revealed reduced synaptophysin immunoreactivity in Pigv(341E) mice, and electrophysiology recordings showed decreased hippocampal synaptic transmission that could underlie impaired memory formation. In single-cell RNA sequencing, Pigv(341E)-hippocampal cells exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction in Abl1 transcript levels in several cell clusters suggested a link to the signaling pathway of GPI-anchored ephrins. We also observed elevated levels of Hdc transcripts, which might affect Histamine Metabolism with consequences for circadian rhythm. This mouse model will not only open the doors to further investigation into the pathophysiology of GPIBD, but will also deepen our understanding of the role of GPI-anchor–related pathways in brain development

  • A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions
    'Cold Spring Harbor Laboratory', 2020
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Voigt A., Mattei D., Knaus A., Moreno Velasquez L., Long M., Vogt G.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect Histamine Metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

Mattei Daniele - One of the best experts on this subject based on the ideXlab platform.

  • A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions.
    'Proceedings of the National Academy of Sciences', 2021
    Co-Authors: Rodríguez De Los Santos, Miguel, Rivalan Marion, David, Friederike S, Stumpf Alexander, Pitsch Julika, Tsortouktzidis Despina, Velasquez, Laura Moreno, Voigt Anne, Schilling Karl, Mattei Daniele
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available. Therefore, we used CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, Pigv:c.1022C \u3e A (p.A341E), at a site that is conserved in mice. Mirroring the human pathology, mutant Pigv 341E mice exhibited deficits in motor coordination, cognitive impairments, and alterations in sociability and sleep patterns, as well as increased seizure susceptibility. Furthermore, immunohistochemistry revealed reduced synaptophysin immunoreactivity in Pigv 341Emice, and electrophysiology recordings showed decreased hippocampal synaptic transmission that could underlie impaired memory formation. In single-cell RNA sequencing, Pigv 341E-hippocampal cells exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction in Abl1 transcript levels in several cell clusters suggested a link to the signaling pathway of GPI-anchored ephrins. We also observed elevated levels of Hdctranscripts, which might affect Histamine Metabolism with consequences for circadian rhythm. This mouse model will not only open the doors to further investigation into the pathophysiology of GPIBD, but will also deepen our understanding of the role of GPI-anchor-related pathways in brain development

Vogt G. - One of the best experts on this subject based on the ideXlab platform.

  • A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions
    'Cold Spring Harbor Laboratory', 2020
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Voigt A., Mattei D., Knaus A., Moreno Velasquez L., Long M., Vogt G.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect Histamine Metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

Stumpf A. - One of the best experts on this subject based on the ideXlab platform.

  • A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions
    'Proceedings of the National Academy of Sciences', 2021
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Pitsch J., Tsortouktzidis D., Velasquez L.m., Voigt A., Schilling K., Mattei D.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available. Therefore, we used CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, Pigv:c.1022C > A (p.A341E), at a site that is conserved in mice. Mirroring the human pathology, mutant Pigv(341E) mice exhibited deficits in motor coordination, cognitive impairments, and alterations in sociability and sleep patterns, as well as increased seizure susceptibility. Furthermore, immunohistochemistry revealed reduced synaptophysin immunoreactivity in Pigv(341E) mice, and electrophysiology recordings showed decreased hippocampal synaptic transmission that could underlie impaired memory formation. In single-cell RNA sequencing, Pigv(341E)-hippocampal cells exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction in Abl1 transcript levels in several cell clusters suggested a link to the signaling pathway of GPI-anchored ephrins. We also observed elevated levels of Hdc transcripts, which might affect Histamine Metabolism with consequences for circadian rhythm. This mouse model will not only open the doors to further investigation into the pathophysiology of GPIBD, but will also deepen our understanding of the role of GPI-anchor–related pathways in brain development

  • A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions
    'Cold Spring Harbor Laboratory', 2020
    Co-Authors: Rodríguez De Los Santos, M., Rivalan M., David F.s., Stumpf A., Voigt A., Mattei D., Knaus A., Moreno Velasquez L., Long M., Vogt G.
    Abstract:

    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect Histamine Metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development