CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control

Lau, Cia-Hin; Suh, Yousin

doi:10.1007/s00335-017-9727-2

Cited by 6 publications

(2 citation statements)

References 127 publications

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“…AIS-CRM∆ mice were created using CRISPR-Cas9 genome-editing technology. RNA-guided nucleases cleave DNA phosphodiester bonds at specific sites in the genome, resulting in the deletion or insertion of these regions [ 43 ]. The AIS-CRM∆ mouse line removed 189 bp of the mouse genomic region corresponding to the AIS risk SNP rs11190870 ( Figs 1B and 3A ).…”

Section: Resultsmentioning

confidence: 99%

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

McCallum-Loudeac,

Moody,

Williams

et al. 2024

Human Molecular Genetics

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Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%–5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.

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Section: Resultsmentioning

confidence: 99%

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

McCallum-Loudeac,

Moody,

Williams

et al. 2024

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…AIS-CRM∆ mice were created using CRISPR-Cas9 genome-editing technology, in which RNA-guided nucleases can edit insertions and deletions into specific sites within a genome (Lau and Suh, 2018). The AIS-CRM∆ mouse line removes 189 bp in the mouse genomic region corresponding to the AIS risk SNP rs11190870 (Fig.…”

Section: Gene Expression Changes In the Ais-crm∆ Mouse Linementioning

confidence: 99%

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

McCallum-Loudeac

Moody

Johnstone

et al. 2023

Preprint

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Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2-5.2 percent of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to better understand the biological cause of AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not onlyLbx1but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region

show abstract

Expression and hydroxyurea-triggered induction of EGFP upon CRISPR/Cas9-mediated integration into the γ-globin gene of K562 cells

et al. 2019

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CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control

Cited by 6 publications

References 127 publications

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice

Expression and hydroxyurea-triggered induction of EGFP upon CRISPR/Cas9-mediated integration into the γ-globin gene of K562 cells

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