Functional analysis of the tumour suppressor gene PTEN in murine B cells and keratinocytes.
To investigate the roles of the PTEN (phosphatase and tensin homologue deleted from chromosome 10)/PI3K (phosphoinositide 3-kinase) signalling pathway in vivo, we have generated a series of mutant mice with null or tissue-specific gene-targeted deletions of Pten. Here we present our investigations of Pten function in B cells and keratinocytes in mice. Mice with a B cell-specific mutation of Pten showed increased serum autoantibodies and elevated numbers of B1a cells. Among conventional B (B2) cells in mutant spleens, numbers of marginal zone B cells were significantly increased, while those of follicular B cells were reciprocally decreased. Immunoglobulin class switch recombination was defective and associated with impaired induction of activation-induced cytidine deaminase. Mice with a keratinocyte-specific mutation of Pten exhibited epidermal hyperplasia, hyperkeratosis and accelerated skin morphogenesis. Within 3 weeks of birth, 90% of these animals died of malnutrition, possibly caused by hyperkeratosis of the oesophageal epithelia. Surviving mutant mice developed spontaneous skin tumours within 8.5 months of birth, and chemical treatment accelerated the onset of tumours. Our data show that PTEN is an important regulator in B cells and keratinocytes.
Suzuki
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Department of Molecular Biology, Akita University School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. suzuki@med.akita-u.ac.jp
Sasaki
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Mak
T W
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Nakano
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D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D051059:PTEN Phosphohydrolase; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology*
D025521:Tumor Suppressor Proteins; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse