Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene.
EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1 alpha promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 -- possible heterodimeric partners for EAT in the anti-apoptotic process -- were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.
Matsushita
Kenichi
K
Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Okita
Hajime
H
Suzuki
Atsushi
A
Shimoda
Kouji
K
Fukuma
Mariko
M
Yamada
Taketo
T
Urano
Fumihiko
F
Honda
Takahiro
T
Sano
Makoto
M
Iwanaga
Shiro
S
Ogawa
Satoshi
S
Hata
Jun-ichi
J
Umezawa
Akihiro
A
D007516:Adenoma, Islet Cell / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D048429:Cell Size; D019254:Genes, bcl-2; D006801:Humans; D006965:Hyperplasia / Q000209:etiology* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
D007328:Insulin; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2