Point Mutation Knockin Cell Lines
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A point mutation Knockin cell line defines a model in which one or more nucleotides are constitutively mutated.
The insertion, deletion, nonsense and sense mutations alter the amino acid sequence of a given protein, thus changing its functions or properties.
Typical applications for point mutation Knockin cell lines
For academic research:
For bio-pharmaceutical research & development:
Strengths and limitations of point mutation Knockin cell lines
- High physiological relevancy of the scientific data obtained from the model (regulatory elements conserved, under control of endogenous promoter, expression of all splice variants, etc.) = more relevant than classical KO where the protein is absent
- Reliable since each cell line is matched with an isogenic control cell clone
- Unpredicted alteration of splicing or 3D-protein structure
→ If the genetic modification creates a dominant mutation, an overexpression of the point mutant in a safe harbor site (Quick Knockin™), might be a valuable option
Burgener AV1, Bantug GR, Meyer BJ, Higgins R, Ghosh A, Bignucolo O, Ma EH, Loeliger J, Unterstab G, Geigges M, Steiner R, Enamorado M, Ivanek R, Hunziker D, Schmidt A, Müller-Durovic B, Grählert J, Epple R, Dimeloe S, Lötscher J, Sauder U, Ebnöther M, Burger B, Heijnen I, Martínez-Cano S, Cantoni N, Brücker R, Kahlert CR, Sancho D, Jones RG, Navarini A, Recher M, Hess C.
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.
Nat Immunol. 2019 Oct.
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