Conditional knockout in mice reveals the critical roles of Ppp2ca in epidermis development
Open accessAbstract
The epidermis is an important tissue in Homo sapines and other animals, and an abnormal epidermis will cause many diseases. Phosphatase 2A (PP2A) is an important serine and threonine phosphatase. The α isoform of the PP2A catalytic subunit (Ppp2ca gene encoding PP2Acα) is critical for cell proliferation, growth, metabolism and tumorigenesis. However, to date, no study has revealed its roles in epidermis development. To specifically investigate the roles of PP2Acα in epidermis development, we first generated Ppp2ca(flox/flox) transgenic mice, and conditionally knocked out Ppp2ca in the epidermis driven by Krt14-Cre. Our study showed that Ppp2ca(flox/flox); Krt14-Cre mice had significant hair loss. In addition, histological analyses showed that the morphogenesis and hair regeneration cycle of hair follicles were disrupted in these mice. Moreover, Ppp2ca(flox/flox); Krt14-Cre mice had smaller size, melanin deposition and hyperproliferation at the base of the claws. Accordingly, our study demonstrates that PP2Acα plays important roles in both hair follicle and epidermis development. Additionally, the Ppp2ca(flox/flox) mice generated in this study can serve as a useful transgene model to study the roles of PP2Acα in other developmental processes and diseases.
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These mice displayed significant hair loss, a thicker epidermis with more fat cells, prominent melanin deposition in the paws and at the base of the claws and tail, and excessive keratinization of the tail.
“Mice displayed significant hair loss, had a thicker epidermis with more fat cells, prominent melanin deposition in the paws and at the base of the claws and the tail, and excessive keratinization of the tail.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
Abnormal hair follicle morphogenesis occurred from the first post-natal hair cycle onwards, characterized by failure of hair cycling and a differentiation defect of matrix cells into the inner root sheath and hair shaft.
“Abnormal hair follicle morphogenesis occurred from the first post-natal hair cycle onwards, and was characterized by failure of hair cycling and a differentiation defect of matrix cells into the inner root sheath and hair shaft.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
Epidermal-specific loss of Cα resulted in smaller animals with aberrant hair morphogenesis and disruption of the hair follicle regeneration cycle.
“Epidermal-specific loss of Cα resulted in smaller animals with aberrant hair morphogenesis and disruption of the hair follicle regeneration cycle [89].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
Some animals had severe stool obstruction, and 15% of mice died at 4-6 weeks of age.
“Some animals had severe stool obstruction, and 15% of mice died at 4-6 weeks of age [89].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
This was associated with decreased phosphorylation of AKT at Thr308 and Ser473.
“this was associated with decreased phosphorylation of AKT (Thr308 and Ser473) [89].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
Histologic examination of the epidermis showed hyperproliferation of basal cells, as witnessed by increased Ki67 expression.
“Upon histologic examination of the epidermis, a hyperproliferation of the basal cells was noted, as witnessed by increased expression of Ki67.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [89]
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Physiologic functions of PP2A: Lessons from genetically modified mice
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- Authors
- Fang, C., Li, L., & Li, J.
- Affiliations
- Nanjing Medical University (CN)
- Yancheng First People's Hospital (CN)
- Model Animal Research Center (CN)
- Corresponding author
- Li, Jianmin
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2016-05-18
- Volume
- 17
- Issue
- 5
- Pages
- 756
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC4881577
- OpenAlex
- W2406512701
- Cited by
- 15
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81100413)
- Nanjing Medical University
- Northwest Fisheries Science Center
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- PPP2CA, epidermal development, hair follicle morphogenesis, hair regrowth, hair loss, conditional knockout, melanin deposition, protein phosphatase 2A
- MeSH terms
- Alopecia, Animals, Epidermis, Mice, Transgenic, Morphogenesis, Mice, Knockout, Hair Follicle, Models, Animal, Mice, Protein Phosphatase 2
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