Modelling human immune deficiency from novel missense mutations with orthologous heterozygous mutations engineered in mice by CRISPR/Cas9

Bahar Miraghazadeh, Chelisa Cardinez, Elizabeth da Silva, Rochna Chand, Ainsley Davies, Gaetan Burgio, Carola Vinuesa, Matthew Cook

    Research output: Contribution to journalMeeting Abstractpeer-review


    Introduction/Background: Next generation sequencing has resulted in substantial progress in identification of Mendelian immune deficiency syndromes. In some cases, however, putative causal mutations occur in single kindreds, or even individual patients. Under these circumstances, functional analysis of patient derived cells combined with in vitro analysis of genetically manipulated cell lines can provide additional evidence in support of genetic causation, but this might not be conclusive. Objectives: Understanding how genetic defects result in complex syndromes of immune deficiency and immune dysregulation can be impossible to achieve in vitro. One method for overcoming these obstacles is to generate accurate mouse models of human immune deficiency Methods: Mouse models of human immune deficiency are a valuable tool in which the murine genome is engineered to introduce a mutation orthologous to that discovered in the patient. We have applied this strategy to elucidate causation and mechanism of immunological defect in several mutations affecting the NF-kB pathway. Results: So far, defects in both canonical and non-canonical pathways of NF-kB activation have been shown to cause immune deficiency, often associated with immune dysregulation. We describe a known defects and novel putative defect identified in the canonical NF-kB pathway Conclusions: CRISPR-cas9 mouse models can be used to elucidate mechanism of disease and provide compelling evidence that mutations are causative.
    Original languageEnglish
    Pages (from-to)440-440
    JournalJournal of Clinical Immunology
    Issue number3
    Publication statusPublished - 2018
    EventCIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference, IMDDNAC 2018 - Toronto, Canada, Canada
    Duration: 1 Jan 2018 → …


    Dive into the research topics of 'Modelling human immune deficiency from novel missense mutations with orthologous heterozygous mutations engineered in mice by CRISPR/Cas9'. Together they form a unique fingerprint.

    Cite this