Related Experiment Video
Updated: Aug 11, 2026
07:07
Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
Published on: February 21, 2016
Unexpected Cartilage Phenotype in CD4-Cre-Conditional SOS-Deficient Mice
Geoffrey Guittard1, Devorah L Gallardo2, Wenmei Li1
1Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH , Bethesda, MD , USA.
Frontiers in Immunology
|April 8, 2017
Summary
Genetic disruption of SOS1 and SOS2 in mice leads to unexpected joint nodules and dysfunction, originating from dysplastic chondrocytes. This highlights potential off-target effects of CD4-Cre and implicates RAS signaling in joint development.
Area of Science:
- Cell Biology
- Immunology
- Genetics
Background:
- RAS signaling pathways are crucial for cellular functions, with SOS proteins activating RAS.
- Investigating SOS protein roles in T cell biology is essential for understanding immune responses.
Purpose of the Study:
- To investigate the role of SOS proteins in T cell biology using a CD4-Cre mediated gene deletion model.
- To characterize the unexpected joint phenotype observed in mutant mice.
Main Methods:
- Generation of conditional knockout mice (Sos1f/fSos2) crossed with CD4-Cre transgenic mice.
- Histological analysis and second harmonic generation imaging of joint tissues.
- Phenotypic assessment including joint mobility and physical examination.
Main Results:
- Over 90% of mutant mice developed joint nodules, particularly in carpal joints, by 5 months of age.
- Progressive joint stiffness, hind limb paralysis, and lameness were observed with age.
- Histology revealed dysplastic chondrocytes as the source of abnormal joint growth, encased in collagen networks.
- The phenotype was independent of RAG2, indicating T cell receptor rearrangement is not required.
Conclusions:
- CD4-Cre expression in non-immune cells, such as chondrocytes, likely mediates the observed joint phenotype.
- Disruptions in the RAS signaling pathway are strongly implicated in causing this phenotype.
- The study serves as a cautionary note regarding the use of CD4-Cre mice for specific gene deletion in conventional T cells due to potential off-target effects.
