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Construction and Analysis of an Allelic Series of Ccn1 Knockin Mice
Ricardo I Monzon1, Ki-Hyun Kim2, Lester F Lau3
1Department of Biological Sciences, Saint Xavier University, 3700 W. 103rd Street, Chicago, IL, 60655, USA.
Abstract:
The embryonic lethality of mice with conventional global knockout of Ccn1 (Cyr61) precludes analysis of Ccn1 functions in late embryonic development or in adulthood. To circumvent this limitation, we have generated conditional knockout mice that allow cell type-specific deletion of Ccn1, and constructed an allelic series of Ccn1 knockin mice that express CCN1 defective for binding specific integrins in lieu of the wild type protein. Here we describe the construction of these mice and discuss how analysis of these animals can provide unique insights into Ccn1 functions mediated through specific integrin receptors. It is anticipated that future analysis of mice carrying specific mutations in genes of the Ccn family will be greatly facilitated by application of the CRISPR/Cas9 gene editing methodology.
Insights
Researchers created novel conditional knockout and knockin mouse models to study Cyr61 (CCN1) protein functions. These models overcome embryonic lethality, enabling research into Cyr61
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Global knockout of Cyr61 (CCN1) in mice results in embryonic lethality, preventing the study of its roles in later development.
- Understanding Cyr61's specific functions requires models that allow for targeted genetic manipulation.
Purpose of the Study:
- To generate and characterize conditional knockout and knockin mouse models for Cyr61 (CCN1).
- To enable the investigation of Cyr61 functions in a cell type-specific manner and through interactions with integrins.
Main Methods:
- Generation of conditional knockout mice for cell type-specific deletion of Ccn1.
- Construction of an allelic series of Ccn1 knockin mice expressing altered CCN1 protein.
- Utilizing CRISPR/Cas9 gene editing for future Ccn family studies.
Main Results:
- Successfully created conditional knockout and knockin mouse models for Cyr61 (CCN1).
- These models allow for the circumvention of embryonic lethality associated with global Ccn1 knockout.
Conclusions:
- The developed mouse models provide unique insights into Cyr61 (CCN1) functions mediated by specific integrin receptors.
- These models are valuable tools for studying Ccn family gene functions in a spatially and temporally controlled manner.
