Navigation Links
St. Jude finds clues to hearing loss from chemotherapy

Children with cancer who suffer hearing loss due to the toxic effects of chemotherapy might one day be able to get their hearing back through pharmacological and gene therapy, thanks to work done with mouse models at St. Jude Children's Research Hospital. Mice with a variety of genetic mutations that disrupt different parts of the ear will also help scientists understand age-related hearing loss in adults, as well as hearing loss caused by long-term exposure to loud noise, according to the researchers.

The investigators took the first step toward these ambitious goals by identifying 17 families of mice whose offspring carry one or more of a variety of mutations that cause them to lose the ability to hear high-frequency sounds, according to Jian Zuo, Ph.D., associate member of the St. Jude Department of Developmental Neurobiology. Zuo is senior author of a report on this work that appears in the October issue of Hearing Research.

These models will help scientists understand what happens in the ears of children who suffer ototoxicity (toxic damage to the inner ear due to chemotherapy) and eventually, which genes are responsible for that damage. "Our ongoing study of these mouse models will advance understanding of age-related and noise-induced hearing loss in humans--such as long-term exposure to loud music--which are similar to the damage that occurs in children receiving chemotherapy," Zuo said.

The mouse models of hearing loss were produced by the Tennessee Mouse Genome Consortium, a group of institutions across Tennessee that includes universities, several medical research centers and a national laboratory.

The consortium used ENU, a chemical that causes random mutations in sperm of mice that were subsequently mated with females. Offspring of this mating carried mutations in one or more specific spots in their DNA, Zuo explained. The random mutations caused a variety of disruptions of normal functions. However, only some of the mutat ions were likely to cause hearing loss, and it was not known which mutation each mouse had. Therefore, the St. Jude team screened more than 1,800 mice from 285 families using an auditory brainstem responses test. This test determines whether a particular mouse can respond to high frequencies by recording electrical activity from the hearing nerve and other parts of the brain in response to brief, high-frequency sounds. The team identified 17 families that showed evidence of hearing loss. The investigators then determined the types of ear abnormalities the mice had. The goal was to find the genes involved in different aspects of hearing loss.

"Now that we've identified the various problems in the ear that can contribute to hearing loss in these models, we can work back and look for specific mutations in these animals," Zuo said. "That will let us link specific mutations to specific disruptions in the ear that cause hearing loss. The long-term goal is to try to manipulate or replace those genes in order to overcome those problems."

Individual mutations might disrupt the work of a cascade of genes that cooperate to construct certain nerves or sections of the inner ear that sense sound; that stimulation is then turned into electrical impulses that go to the hearing center of the brain. Understanding how a specific mutation disrupts that cascade might lead to ways to repair the damage, Zuo said.

For example, one type of damage that occurs in children whose hearing is damaged by chemotherapy is loss of hair cells in the inner part of the ear. These cells sprout extremely fine hairs that move in response to sound waves and set up the electrical impulse that goes into the brain. These are the same cells damaged in adults by prolonged exposure to loud noise. "In the future we'd like to be able to prevent the loss of these hair cells or trigger their re-growth with some form of pharmacological or gene therapy intervention," Zuo said.

Source:Proceedings of the National Academy of Sciences (PNAS)

Related biology news :

1. Current human embryonic stem cell lines contaminated UCSD/Salk team finds
2. Study finds more than one-third of human genome regulated by RNA
3. ASU researchers finds novel chemistry at work to provide parrots vibrant red colors
4. Same mutation aided evolution in many fish species, Stanford study finds
5. NC State scientist finds soft tissue in T. rex bones
6. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
7. Genetically modified rice in China benefits farmers health, study finds
8. Survey finds silver contamination in North Pacific waters
9. Anti cancer virotherapy well tolerated in first human administration, research finds
10. NASA study finds snow melt causes large ocean plant blooms
11. Oceans more vulnerable to agricultural runoff than previously thought, study finds

Post Your Comments:

(Date:10/29/2015)... 29, 2015   MedNet Solutions , an innovative ... of clinical research, is pleased to announce that it ... (MHTA) as one of only three finalists for a ... Small and Growing" category. The Tekne Awards honor ... superior technology innovation and leadership. iMedNet™ ...
(Date:10/29/2015)... , Oct. 29, 2015  Rubicon Genomics, ... for U.S. distribution of its DNA library preparation ... and Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq ... the preparation of NGS libraries for liquid biopsies--the ... diagnostic and prognostic applications in cancer and other ...
(Date:10/29/2015)... , Oct. 29, 2015 Today, ... announced a partnership with 2XU, a global leader ... deliver a smart hat with advanced bio-sensing technology. ... other athletes to monitor key biometrics to improve ... strategic partnership, the two companies will bring together the ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... Nov. 25, 2015  PharmAthene, Inc. (NYSE MKT: PIP) ... a stockholder rights plan (Rights Plan) in an effort ... carryforwards (NOLs) under Section 382 of the Internal Revenue ... PharmAthene,s use of its NOLs could be substantially ... defined in Section 382 of the Code. In general, ...
(Date:11/25/2015)... and HOLLISTON, Mass. , Nov. ... (Nasdaq: HART ), a biotechnology company developing bioengineered ... Jim McGorry will present at the LD ... 2015 at 2:30 p.m. PT. The presentation will be ... 30 days. Management will also be available at the ...
(Date:11/25/2015)... (PRWEB) , ... November 25, 2015 , ... ... and the Organization of Black Aerospace Professionals (OPBAP) has been formalized with the ... other AMA team leaders met with OPBAP leaders Capt. Karl Minter and Capt. ...
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica Richman and Zachary ... in their initial angel funding process. Now, they are paying it forward to ... early stage investments in the microbiome space. In this, they join other ...
Breaking Biology Technology: