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

361 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 - Apr 26 1994
Externally publishedYes

Fingerprint

Polycystic Kidney Diseases
Lymphopenia
Hair
Hair Color
Lymphocytes
T-Lymphocytes
Kidney
bcl-2 Genes
Ionomycin
Hair Follicle
Lymphocyte Count
Mesoderm
Morphogenesis
Nervous System
Intestines
Interleukin-2
Lipopolysaccharides
Anti-Idiotypic Antibodies
Acetates
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Targeted disruption of Bcl-2αβ in mice : Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. / Nakayama, Keiko; Nakayama, Kei Ichi; Negishi, Izumi; Kuida, Keisuke; Sawa, Hirofumi; Loh, Dennis Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 9, 26.04.1994, p. 3700-3704.

Research output: Contribution to journalArticle

@article{8baf95aacda045ec92432925329355c5,
title = "Targeted disruption of Bcl-2αβ in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia",
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.",
author = "Keiko Nakayama and Nakayama, {Kei Ichi} and Izumi Negishi and Keisuke Kuida and Hirofumi Sawa and Loh, {Dennis Y.}",
year = "1994",
month = "4",
day = "26",
doi = "10.1073/pnas.91.9.3700",
language = "English",
volume = "91",
pages = "3700--3704",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

TY - JOUR

T1 - Targeted disruption of Bcl-2αβ in mice

T2 - Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia

AU - Nakayama, Keiko

AU - Nakayama, Kei Ichi

AU - Negishi, Izumi

AU - Kuida, Keisuke

AU - Sawa, Hirofumi

AU - Loh, Dennis Y.

PY - 1994/4/26

Y1 - 1994/4/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028175759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028175759&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.9.3700

DO - 10.1073/pnas.91.9.3700

M3 - Article

C2 - 8170972

AN - SCOPUS:0028175759

VL - 91

SP - 3700

EP - 3704

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -