-実験動物開発室-

Autophagy monitoring congenic strains

GFP-LC3#53 (RBRC00806)

C.B6D2-Tg(CAG-GFP/LC3)53Nmz/Rbrc (RBRC01413)

C3.B6D2-Tg(CAG-GFP/LC3)53Nmz/Rbrc (RBRC01414)

MSM.B6D2-Tg(CAG-GFP/LC3)53Nmz/Rbrc (RBRC01227)

(avi file:12074KB/2s)

Courtesy of Noboru Mizushima, M.D., Ph.D.

Autophagy (Greek for “self-eating”) is known to have important roles in various physiological and pathological processes such as maintenance of the amino acid pool during starvation, preimplantation development, prevention of neurodegeneration, anti-aging, tumor suppression, clearance of intracellular microbes, and regulation of innate and adaptive immunity [1,2]. Accordingly, there is a growing need among scientists to be able to detect autophagy in vivo. The GFP-LC3#53 transgenic mouse is one of the most widely used in vivo autophagy monitoring tools and was developed by Dr. Noboru Mizushima [3]. This transgenic mouse enables the accurate detection of autophagosome in diverse biological processes. We have extended its capability to other useful inbred strains such as BALB/cAnN (RBRC00641), C3H/HeNCrlj, and MSM/MsRbrc (RBRC00209) by successive backcrossing. The genetic backgrounds of these strains were examined using simple sequence length polymorphism markers to assess congenic status. A genotyping protocol was also established to distinguish homozygous and hemizygous transgenic mice. These autophagy monitoring mice will be useful for assessing autophagy in various mouse disease models.

Atg7 deletion in various tissues

B6.Cg-Atg7<tm1Tchi> (RBRC02759)

B6.Cg-Atg7<tm1.1Tchi> (RBRC02760)

Courtesy of Masaaki Komatsu, Ph.D.

To investigate the physiological roles of autophagy in mice, conditional knockout mice for an autophagy-essential gene, Atg7, were generated. A number of groups have generated various tissue-specific autophagy-deficient mice. Many of the molecular mechanisms underpinning autophagy and the physiologic roles of these processes have since been elucidated.

Autophagy is a pathway for bulk protein degradation that has been conserved in most eukaryotic cells. The initial steps of autophagy include the formation and elongation of the isolation membrane. This membrane enwraps organelles and other cytoplasmic components until forming a double-membrane vesicle called an autophagosome. The biogenesis of autophagosomes requires proteins encoded by autophagy-related (Atg) genes, most of which were initially identified in yeast. To date, Atg5 conditional knockout mice, GFP-tagged Map1lc3a Tg mice (mammalian homologue of Atg8p), and other various Atg-deficient mice have been established [1].
While autophagy has been considered a non-selective process, growing evidence indicates that selectivity of autophagy plays an important role in the turnover of aberrant proteins, disposal of damaged organelles, and elimination of protein aggregates and invading pathogens. Tissue-specific Atg7-deficient mice exhibit liver injury, diabetes, muscle atrophy, and neurodegeneration [2–4]. Conventional and conditional Atg7 knockout mice provide the opportunity to understand the role of autophagy in homeostasis and various common diseases.