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Updated: Mar 21, 2026
Identification of the Genes Involved in Stomatal Development via Epidermal Phenotype Scoring
Published on: January 20, 2023
C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
Mette Camilla Kriegbaum1,2, Benedikte Jacobsen1,2, Annette Füchtbauer3
1The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Abstract:
C4.4A is a modular glycolipid-anchored Ly6/uPAR/α-neurotoxin multidomain protein that exhibits a prominent membrane-associated expression in stratified squamous epithelia. C4.4A is also expressed in various solid cancer lesions, where high expression levels often are correlated to poor prognosis. Circumstantial evidence suggests a role for C4.4A in cell adhesion, migration, and invasion, but a well-defined biological function is currently unknown. In the present study, we have generated and characterized the first C4.4A-deficient mouse line to gain insight into the functional significance of C4.4A in normal physiology and cancer progression. The unchallenged C4.4A-deficient mice were viable, fertile, born in a normal Mendelian distribution and, surprisingly, displayed normal development of squamous epithelia. The C4.4A-deficient mice were, nonetheless, significantly lighter than littermate controls predominantly due to differences in fat mass. Congenital C4.4A deficiency delayed migration of keratinocytes enclosing incisional skin wounds in male mice. In chemically induced bladder carcinomas, C4.4A deficiency attenuated the incidence of invasive lesions despite having no effect on total tumour burden. This new C4.4A-deficient mouse line provides a useful platform for future studies on functional aspects of C4.4A in tumour cell invasion in vivo.
Insights
The C4.4A protein deficiency in mice resulted in reduced body fat and delayed skin wound healing. C4.4A-deficient mice also showed fewer invasive bladder tumors, suggesting a role in cancer progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- C4.4A is a membrane-associated protein found in squamous epithelia and solid cancers, linked to poor prognosis.
- Its precise biological function in cell adhesion, migration, and invasion remains unclear.
Purpose of the Study:
- To generate and characterize the first C4.4A-deficient mouse model.
- To investigate the functional significance of C4.4A in normal physiology and cancer progression.
Main Methods:
- Generation and characterization of C4.4A-deficient mice.
- Assessment of physiological parameters including body mass and fat content.
- Evaluation of keratinocyte migration in skin wound healing models.
- Analysis of tumor incidence and invasiveness in chemically induced bladder carcinomas.
Main Results:
- C4.4A-deficient mice were viable, fertile, and exhibited normal squamous epithelia development.
- Mice lacking C4.4A showed reduced body weight, primarily due to lower fat mass.
- Keratinocyte migration was delayed in male C4.4A-deficient mice during skin wound closure.
- Bladder carcinoma incidence of invasive lesions was attenuated in C4.4A-deficient mice, without affecting overall tumor burden.
Conclusions:
- C4.4A plays a role in regulating body fat and keratinocyte migration.
- C4.4A deficiency attenuates the invasiveness of bladder carcinomas.
- The generated C4.4A-deficient mouse line is a valuable tool for studying C4.4A's role in tumor cell invasion.
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