腫瘍抑制遺伝子Brca1は,マウスにおける胚細胞増殖に必須である
R Hakem1, J L de la Pompa, C Sirard
1Amgen Institute, Toronto, Ontario, Canada.
Cell
|June 28, 1996
まとめ
BRCA1遺伝子の変異は,がんと関連しています. ホモジゴス Brca1変異性マウス胚は適切に発達できず,細胞増殖の障害により胚形成の初期に死亡します.
科学分野:
- 発達生物学 発達生物学とは
- 遺伝学 遺伝学とは
- がん研究 がん研究
背景:
- BRCA1遺伝子の変異は,ヒトにおける遺伝性乳がんおよび卵巣がんと関連しています.
- Brca1+/-マウスは生存可能であり,11ヶ月になるまで腫瘍を発症しない.
研究 の 目的:
- ホモジゴス Brca1 変異の胚性致死性を調査する.
- Brca1変異体における胚発達の欠陥の基礎となる細胞メカニズムを理解する.
主な方法:
- ホモジゴス Brca1 (((5-6) ミュータントマウスの生成と分析.
- 細胞増殖とアポトーシスアッセイを含む胚の発達に関するインビボおよびインビトロ研究.
- シクリンE,mdm-2,p21.を含む遺伝子発現の分析
主要な成果:
- ホモジゴス Brca1 (((5-6) 変異胚は,胚形成の7.5日前に発達障害を示し,メソデーム形成が損なわれ,異常な胚外発達がある.
- ミュータント胚は,細胞増殖の減少とサイクリンEとmdm-2の発現の減少,p21発現の劇的な増加を示しています.
- 実験室内試験では,突然変異した胚の芽細胞の成長が著しく低下していることが確認されました.
結論:
- 胃化の前のBrca1(5-6) ミュータントマウスの胚性致死性は,生殖層の発達に不可欠な増殖爆発の失敗によって引き起こされる可能性が高い.
- BRCA1は,早期の胚細胞増殖と発達において重要な役割を果たしており,がんの予備性に関連したDNA修復におけるその役割とは独立しています.
関連する概念動画
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:43Mouse Models of Cancer Study
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...