ネズミのリセシブ多囊性腎臓病を引き起こす変異に関連した候補遺伝子
J H Moyer1, M J Lee-Tischler, H Y Kwon
1University of Tennessee Graduate School of Biomedical Sciences, Biology Division, Oak Ridge National Laboratory, TN 37831-8077.
Science (New York, N.Y.)
|May 27, 1994
まとめ
ヒトの自己相性後退性多囊性腎疾患 (PKD) を模倣する変異を有するトランス遺伝子マウスを開発した. これらのマウスは多囊性腎臓と肝臓の病変を示し,細胞サイクル制御に関連する新しいPKD遺伝子の識別に役立ちます.
科学分野:
- 遺伝学と分子生物学について
- ネフロロジーはネフロロジーを用います.
- 発達生物学 発達生物学とは
背景:
- オートソームリセッシブ多囊性腎臓病 (ARPKD) は,重度の遺伝疾患である.
- ARPKDの基礎となる分子メカニズムを理解することは,効果的な治療法の開発に不可欠です.
- 動物モデルは,ARPKDのような複雑な遺伝疾患の研究に不可欠です.
研究 の 目的:
- オートソーマリセッシブ多発性腎臓病 (ARPKD) のマウスモデルを生成し,特徴づけること.
- 生成されたマウスモデルにおけるARPKDフェノタイプに責任を負う遺伝的場所と候補遺伝子を特定する.
- ARPKD.の病原性における細胞周期調節の潜在的な役割を調査する.
主な方法:
- 挿入変異を持つトランスジェニックマウスの生成.
- 腎臓と肝臓の検査を含むホモジゴス型変異性マウスのフェノタイプ分析.
- トランスゲンを分子マーカーとして利用した突然変異の場所のクローニングと特徴付け.
- 候補性多囊性腎臓病 (PKD) 遺伝子の特定と特徴付け
主要な成果:
- ホモジゴス型トランスジェニックマウスは,ヒトのARPKDを模倣した双方の多囊性腎臓と肝臓の損傷を含む複雑な表型を示した.
- ミュータントのロカスがクローン化され,特徴づけられることに成功した.
- 候補PKD遺伝子が特定され,突然変異の場所と関連していることが判明しました.
- 特定された遺伝子の補完DNAは,細胞周期制御に関与するモチーフを持つペプチドを予測した.
結論:
- 生成されたトランスジェニックマウスラインは,ヒトのオートソーマルリセッシブ多発性腎臓病 (ARPKD) を研究するための貴重なモデルとして機能します.
- 新しい候補PKD遺伝子の特定は,ARPKDの分子基盤に関する新しい洞察を提供します.
- 細胞サイクル制御モチーフの存在は,ARPKDの病原性における細胞サイクル不調の潜在的な役割を示唆しています.
関連する概念動画
01:11Genetic Lingo
Overview
01:39Epistasis
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
01:16In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:09Epistasis Analysis
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
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,...