Hokkaido University: Institute for Genetic Medicine

Laboratories

Biomedical Animal Research Laboratory

Identification of the biological mechanisms underlying senescence- and cancer-resistance in naked mole-rat (Heterocephalus glaber)

  • Associate Professor Kyoko Miura, Ph.D.
  • Assistant Professor Yoshimi Kawamura, Ph.D.

The naked mole-rats (NMRs) are small fossorial rodents without hair (approximately 30-60g, Fig 1A). NMRs are the longest living rodent with a maximum lifespan exceeding 30 years. In addition to its longevity, NMRs have an extraordinary resistance to cancer as tumors have never been observed. Now we are studying about the anti-cancer and anti-senescence mechanisms in NMRs with the approaches of molecular biology, cell biology and developmental engineering. Ultimately, we will create “senescence- and cancer-resistant” transgenic mice by introducing selected naked mole-rat genes. Our study would contribute to the development of the novel preventive medicine of cancer and senescence in the future.

Establishment of the basic infrastructure for the biological analyses of NMR

Naked mole-rats (NMR) (Fig. 1A) are wild rodent naturally found in subterranean burrows in the savanna regions of the horn of Africa (Ethiopia, Kenya and Somalia). NMR is one of only two eusocial mammals like ant or bee (Fig. 1B), exhibiting division of labor such as a single breeding ‘queen’, one-to-some ‘king’ and many sterile subordinates (‘solders’ and ‘workers’). Surprisingly, NMR’s maximum lifespan exceeds 30 years although their body size is same of mouse. Moreover, these animals have never been observed any spontaneous tumor formation (N=800), indicating the existence of the species-specific cancer- and senescence-resistant mechanisms. Recently, we have established the facility and the methods for breeding of NMRs (Fig. 1C). We have also generated several cell lines including fibroblasts, immortal cell lines and iPS cells for in vitro analyses. We have also collected the gene expression data sets of several NMR organs and constructed genome and gene expression browser of NMR using next-generation sequencing technologies (cooperation with Iwate Tohoku Medical Megabank Organization, unpublished data). Furthermore, 3D brain atlas of NMR has been constructed using high resolution MRI (Seki, Miura et al., Frontiers in Neuroanatomy, 2013). Based on these results, now we are trying to identify NMR-specific anti-cancer and anti-senescence mechanisms by cell biological approaches and species-comparison of genes expressions using next-generation DNA sequencing technologies (Fig. 2).