alexa Mouse Models of Radiosensitivity | OMICS International
ISSN: 0975-0851
Journal of Bioequivalence & Bioavailability
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Mouse Models of Radiosensitivity

Eugenia M Yazlovitskaya1,2*

1Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, USA

2Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA

*Corresponding Author:
Eugenia M Yazlovitskaya
Department of Medicine, Division of Nephrology
Vanderbilt University Medical Center
Nashville, TN 37232, USA
Tel: 1-615-322-6679
Fax: 1-615-343-7156
E-mail: [email protected]

Received Date: July 22, 2013; Accepted Date: July 24, 2013; Published Date: July 31, 2013

Citation: Yazlovitskaya EM (2013) Mouse Models of Radiosensitivity. J Bioequiv Availab 5:e36. doi: 10.4172/jbb.10000e36

Copyright: © 2013 Yazlovitskaya EM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Bioequivalence & Bioavailability

Ionizing radiation (IR) is a known environmental, medical, and military hazard that can produce dreadful health impairments. At the molecular and cellular level, radiation toxicity paradigm defines DNA damage as the most critical biological effect inferred by IR [1,2]. Specifically, IR produces clustered DNA damage, particularly doublestrand DNA breaks (DSBs). Signal transduction pathways and DNA repair systems are activated in response to IR to protectcells from injury. Discovery of radiosensitive human diseases has revealed two disease classes consistent with the distinct biological responses to IR: recognition of DSBs and repair of DSBs.

After tumor irradiation, the patients with one class of radiosensitive diseases developed severe dermatitis and deep tissue necrosis. This disease class includes ataxia-telangiectasia (AT) [3], the Nijmegen breakage syndrome (NBS) [4], ataxia-telangiectasia-like disorder (ATLD) [5] and Nijmegen breakage syndrome-like disorder (NBSLD) [6]. Genes responsible for these disorders have been identified as ATM for AT, NBS1 for NBS, MRE11A for ATLD and RAD50 for NBSLD [7]. Proteins encoded by these genes are all required for checkpoint response, a signal transduction pathway that recognizes DSBs [8].

Another class of radiosensitive diseases exhibits severe combined immunodeficiency (SCID), and the responsible genes are DNA-PKcs, Artemis and LIG4 (DNA ligase IV) [9]. Proteins encoded by these genes are involved in the repair of DSBs viaa process called non-homologous end-joining (NHEJ) [10].

Identification of genes responsible for radiosensitive diseases allowed for development of radiosensitive mouse models. Mice deficient in Atm were created for targeting the checkpoint response [11]. However, inactivation of Mre11, Rad50, or Nbs1 led to early embryonic lethality, allowing only for models with conditional knockout of these genes. In addition to MRN complex (Mre11, Rad50 and Nbs1) which recognizes DSB end and recruits ATM, other proteins are essential for IR-induced checkpoint and cell cycle arrest including H2AX and p53 [12]. Mice deficient in these proteins also demonstrate increased radiosensitivity [13]. SCID mouse models represent genes involved in IR-induced DSB repair through NHEJ [14].

Studies of mouse models of radiosensitive diseases demonstrated that immunodeficiency and elevated risk of leukemia/lymphoma associated with radiosensitivity is attributed to defects in DNA damage response and repair mechanisms acquired during development of the immune system. In the absence of checkpoint response, the risk of abnormal end joining of broken DNA is increased. Without NHEJ, the DSBs must be repaired by other less specific mechanisms to insure cell survival thus increasing probability of errors. Consequently, accumulation of cells with the abnormal DNA rearrangements may increase the risk of developing lymphoma/leukemia.

The most recent studies of molecular mechanisms underlying IRinduced cell death emphasize multiple pathways regulating cellular response to IR beyond DNA damage and repair. These pathways include membrane-dependent signaling pathways and by stander effect, a process of cellular response to irradiation of the neighboring cells rather than to direct IR exposure [15]. Targeting proteins regulating these pathways opens new avenues for development of new animal models of radiosensitivity. One recent example is a knockout of mitochondrial tumor suppressor Fus1 in mice. This model demonstrated novel radioprotective function for Fus1 whichmodulates radiosensitivity of normal tissues via regulation of anti-oxidant response pathways [16]. Interestingly, Fus1-deficient mice had increased frequency of spontaneous tumors and immunologic disorders [17,18], consistent with the mechanistic link of radiosensitivity to abnormal immune functions and increased risk of cancer.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11702
  • [From(publication date):
    September-2013 - Feb 19, 2018]
  • Breakdown by view type
  • HTML page views : 7924
  • PDF downloads : 3778
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version