Targeted disruption of Bcl-2αβ in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia

Keiko Nakayama, Kei Ichi Nakayama, Izumi Negishi, Keisuke Kuida, Hirofumi Sawa, Dennis Y. Loh

Research output: Contribution to journalArticle

362 Citations (Scopus)

Abstract

Mice carrying ablated coding regions of the bcl-2α and bcl-2β transcripts have been made. bcl-2(-/-) mutants are smaller but viable, although about half of them die by 6 weeks of age. As shown earlier with somatic bcl-2 gene-targeted mice, the number of lymphocytes markedly decreased within few weeks after birth while other hematopoietic lineages remained unaffected. Among lymphocytes, CD8+ T cells disappeared most quickly followed by CD4+ T cells, whereas B cells were least affected. bcl- 2(-/-) lymphocytes, however, could respond normally to various stimuli including anti-CD3, Con A, phorbol 12-myristate 13-acetate plus ionomycin, interleukin 2, lipopolysaccharide, and anti-IgM antibody. Abnormalities among nonlymphoid organs include smaller auricles, hair color turning gray at 4-5 weeks of age, and polycystic kidney disease-like change of renal tubules. These results suggest that Bcl-2 may be involved during morphogenesis where inductive interactions between epithelium and mesenchyme are important such as in the kidneys, hair follicles, and perichondrium of auricles. Surprisingly, the nervous system, intestines, and skin appear normal despite the fact that these organs show high levels of endogenous Bcl-2 expression in normal mice.

Original languageEnglish
Pages (from-to)3700-3704
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number9
DOIs
Publication statusPublished - 1994 Apr 26
Externally publishedYes

ASJC Scopus subject areas

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