The use of non-traditional models in the study of cancer resistance-the case of the naked mole rat.

Non-traditional model organisms are typically defined as any model the deviates from the typical laboratory animals, such as mouse, rat, and worm. These models are becoming increasingly important in human disease research, such as cancer, as they often display unusual biological features. Naked mole rats (NMRs) are currently one of the most popular non-traditional model, particularly in the longevity and cancer research fields. NMRs display an exceptionally long lifespan (~30 years), yet have been observed to display a low incidence of cancer, making them excellent candidates for understanding endogenous cancer resistance mechanisms. Over the past decade, many potential resistance mechanisms have been characterized. These include unique biological mechanisms involved in genome stability, protein stability, oxidative metabolism, and other cellular mechanisms such as cell cycle regulation and senescence. This review aims to summarize the many identified cancer resistance mechanisms to understand some of the main hypotheses that have thus far been generated. Many of these proposed mechanisms remain to be fully characterized or confirmed in vivo, giving the field a direction to grow and further understand the complex biology displayed by the NMR.

Evaluation of the Effect of Chronic 94 GHz Exposure on Gene Expression in the Skin of Hairless Rats In Vivo.

Millimeter waves (MMW) are broadband frequencies that have recently been used in several applications in wireless communications, medical devices and nonlethal weapons [i.e., the nonlethal weapon, Active Denial Systems, (ADS) operating at 94-95 GHz, CW]. However, little information is available on their potential effects on humans. These radio-frequencies are absorbed and stopped by the first layer of the skin. In this study, we evaluated the effects of 94 GHz on the gene expression of skin cells. Two rat populations consisting of 17 young animals and 14 adults were subjected to chronic long-term 94 GHz MMW exposure. Each group of animals was divided into exposed and sham subgroups. The two independent exposure experiments were conducted for 5 months with rats exposed 3 h per day for 3 days per week to an incident power density of 10 mW/cm2, which corresponded to twice the ICNIRP limit of occupational exposure for humans. At the end of the experiment, skin explants were collected and RNA was extracted. Then, the modifications to the whole gene expression profile were analyzed with a gene expression microarray. Without modification of the animal's temperature, long-term chronic 94 GHz-MMW exposure did not significantly modify the gene expression of the skin on either the young or adult rats.

Kyoto rhino rats derived by ENU mutagenesis undergo congenital hair loss and exhibit focal glomerulosclerosis.

N-ethyl-N-nitrosourea (ENU) mutagenesis is an important tool for studying gene function and establishing human disease models. Here, we report the characterization of a novel hairless mutant rat strain that carries a recessive mutation called Kyoto rhino (krh), which was created by ENU-mutagenesis. We produced a F344-krh strain through inbreeding without backcrossing to F344 rats. The krh/krh rats lost their coat hair by eight weeks of age. They also developed wrinkled skin, cystic hair canals and long curved nails by four months of age. Markedly dilated hair follicles that contained keratin debris were observed during histological analysis of the skin. The krh locus was mapped near the hairless (Hr) gene on chromosome 15. Sequence analysis revealed a nonsense mutation (c. 1238 C>A, p. S413X) in the Hr gene. The truncated HR protein was deduced to lack a zinc-finger domain and repression domains. In aged Hr(krh)/Hr(krh) rats, focal glomerulosclerosis (FGS) was observed in which collapsed glomeruli contained protein exudates in Bowman's capsule. Mesangial matrices that had proliferated in segments and foot processes that were fused in podocytes were also observed. The Hr(krh)/Hr(krh) rats also suffered from significant proteinuria. Given its breeding history, the F344-Hr(krh) strain may harbor ENU-induced mutation(s) that underlie FGS in addition to having the Hr(krh) mutation. The F344-Hr(krh) rat is a useful model of skin disease and may provide a new model system for the examination of the pathogenesis of FGS.