Blind Mole Rat

The genus Spalax contains the blind, fossorial, or subterranean mole rats, which are one of several types of rodents that are called "mole rats".[1] The hystricognath mole-rats of the family Bathyergidae are completely unrelated, but some other forms are also in the family Spalacidae. Zokors (subfamily Myospalacinae) and root rats and bamboo rats (subfamily Rhizomyinae) are spalacids sometimes referred to as mole rats. Blind mole rats are in the family Spalacidae, but are unique enough to be given a separate subfamily, Spalacinae. Alternate opinions on taxonomy consider the blind mole-rats to be the only members of the family Spalacidae and rank other spalacid subfamilies as full families. Other authors group all members of the superfamily Muroidea into a single family, Muridae. The Spalacinae contains two genera and eight species. Some authorities treat all species as belonging to a single genus, Spalax.

Spalax mole rats are truly blind.[2] Their very small eyes are completely covered by a layer of skin. Unlike many other fossorial rodents, Spalax mole rats do not have enlarged front claws and do not appear to use their forearms as a primary digging tool. Digging is almost exclusively conducted using their powerful front teeth, which are separated from the rest of the mouth by a flap of skin. When a Spalax mole rat closes its mouth, its incisors are still on the outside. Blind mole rats may have evolved from spalacids that used their front limbs to dig, because their olecranon processes are relatively large relative to the rest of their arms. The olecranon process is a part of the ulna bone where muscles attach, and digging animals tend to have enlarged olecranon processes to provide a large surface for their large and powerful muscles to attach.

Because they are completely blind, blind mole rats have been important laboratory animals in tests on how eyes and eye proteins function. It should be emphasized that although Spalax has only atrophied subcutaneous eyes and it is sightless, its circadian rhythm is kept. Few publications (Avivi et al) have proved that the circadian genes that control the biological clock are expressed in a similar manner as in sighted, aboveground mammals.

Resistance to cancer

Studies on the growth of fibroblasts in vitro of Spalax judaei and Spalax golani showed that the process of necrosis replaces the role of the systematic apoptosis normally used in most organisms. Low-oxygen conditions, such as those common in blind mole rats' burrows, usually cause cells to undergo apoptosis. In adaptation to higher tendency of cell death, Avivi et al have shown that the blind mole rats evolved a mutation in the tumor suppressor protein p53 (Avivi et al, http://www.nature.com/onc/journal/v26/n17/pdf/1210045a.pdf) (which is also used in humans) to prevent cells from undergoing apoptosis. Human cancer patients have similar mutations, and blind mole rats were thought to be more susceptible to cancer because their cells cannot undergo apoptosis. However, after a specific amount of time (within 3 days according to one study), the cells in blind mole rats release interferon-beta (which the immune system normally uses to counter viruses) in response to overproliferation of cells caused by the suppression of apoptosis. In this case, the interferon-beta triggers cells to undergo necrosis, and this mechanism also kills cancer cells in blind mole rats. Because of tumor suppression mechanisms such as this, blind mole rats and other spalacids are resistant to cancer.[3][4][5] The involvement of interferon in the so called concertated cells death of Spalax cells via necrosis (see ref. 4) was highly criticized. Serious questions have been raised on the inconsistent methodology used that led to this speculation [see discussion at: https://bmcbiol.biomedcentral.com/articles/10.1186/1741-7007-11-91; Manov et al, BMC Biology , 2013]. Noteworthy, in this publication Manov et al, BMC Biology , 2013[8] interesting data on Spalax resistance to cancer have been documented:

  • No spontaneous tumors have ever been noticed in blind mole rat, based on observing thousands of individuals along half a century.
  • Inducing cancer with chemical carcinogens that lead to 100% of the expected tumors in mice and rats after 2-6 months, respectively, indicate an extraordinary cancer resistance of Spalax: Only 2 out of 12 animals, and old ones (>10 years old; Spalax can live ~>20 years; 5 times longer than its evolutionary relative, the rat) developed the expected tumor with one of the carcinogens and only after 18 and 30 months.
  • Most intriguing, Spalax cells (fibroblasts), and only Spalax cells, when grown in co-culture with cancer cells from different species, including a wide range of human cancer cells, kill the cancer cells. This is also true when "feeding" the cancer cells with the medium that Spalax cells grew in. Identification of the secreted substance/s by Spalax fibroblasts and the component on cancer cells' membrane they interact with, that lead to the cancer cells' death can open a possibility for finding a general cure to cancer.

See http://evolution.haifa.ac.il/index.php/29-people/personal-websites/77-personal-site-avivi

Classification

Subfamily Spalacinae

References

  1. ^ Macdonald, D., ed. (2006). The Encyclopedia of Mammals. Oxford: Oxford University Books. p. 203. ISBN 0-87196-871-1. 
  2. ^ Lamarck, Jean-Baptiste (1809). Philosophie zoologique ou exposition des considérations relatives à l'histoire naturelle des animaux. 
  3. ^ Saey, Tina Hesman (5 November 2012). "Cancer cells self-destruct in blind mole rats". Science News. Society for Science and the Public. Retrieved 2012. 
  4. ^ Gorbunova, V.; Hine, C.; Tian, X.; Ablaeva, J.; Gudkov, A. V.; Nevo, E.; Seluanov, A. (2012). "Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism". Proceedings of the National Academy of Sciences. 109 (47): 19392-6. doi:10.1073/pnas.1217211109. PMC 3511137 Freely accessible. PMID 23129611.  Retrieved 27 November 2012
  5. ^ Shams, Imad; Manov, Irena; Malik, Assaf; Band, Mark; Avivi, Aaron (2014). Fighting Cancer Underground: Hypoxia Tolerant Spalax Hides the Key for Treatment. The Plant & Animal Genome XXII Conference. 
  6. ^ Old views and new insights: taxonomic revision of the Bukovina blind mole rat, Spalax graecus (Rodentia: Spalacinae). 2013. 
  7. ^ Old views and new insights: taxonomic revision of the Bukovina blind mole rat, Spalax graecus (Rodentia: Spalacinae). 2013. 
8 ^ Irena Manov, Mark Hirsh, Theodore C Iancu, Assaf Malik, Nick Sotnichenko, Mark Band, Aaron Avivi and Imad Shams+ (2013) Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence. BMC Biology [1]

Further reading

  • Jansa, S. A. and M. Weksler (2004). Phylogeny of muroid rodents: relationships within and among major lineages as determined by IRBP gene sequences. Molecular Phylogenetics and Evolution, 31:256-76. doi:10.1016/j.ympev.2003.07.002 PMID 15019624
  • Michaux, J., A. Reyes, and F. Catzeflis (2001). "Evolutionary history of the most speciose mammals: molecular phylogeny of muroid rodents." Molecular Biology and Evolution, 17:280-293.
  • Musser, G. G. and M. D. Carleton (2005). "Superfamily Muroidea." pp. 894-1531 in Wilson, D. E. and D. M. Reeder, eds. Mammal Species of the World: a Taxonomic and Geographic Reference. 3rd ed. Baltimore: Johns Hopkins University Press.
  • Norris, R. W., K. Y. Zhou, C. Q. Zhou, G. Yang, C. W. Kilpatrick, and R. L. Honeycutt (2004). "The phylogenetic position of the zokors (Myospalacinae) and comments on the families of muroids (Rodentia)." Molecular Phylogenetics and Evolution, 31:972-978.
  • Nowak, R. M. (1999). Walker's Mammals of the World, II. London: Johns Hopkins University Press ISBN 978-0-8018-5789-8
  • Steppan, S. J., R. A. Adkins, and J. Anderson (2004). Phylogeny and divergence date estimates of rapid radiations in muroid rodents based on multiple nuclear genes. Systematic Biology, 53:533-553. doi:10.1080/10635150490468701 PMID 15371245
  • Topachevskii, V. A. (1976) Fauna of the USSR. Volume III: Mammals. Issue 3: Mole rats, Spalacidae. New Delhi: Amerind.

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