A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs

Original Article

The Pharmacogenomics Journal advance online publication 20 July 2010; doi: 10.1038/tpj.2010.60

F Han1,4, H Yu1,4, C Tian1, H E Chen1, C Benedict-Alderfer1, Y Zheng1, Q Wang1,5, X Han1 and Q Y Zheng1,2,3

1. Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, USA
2. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
3. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA

Correspondence: Dr QY Zheng, Department of Otolaryngology-HNS, Case Western Reserve University, 11100 Euclid Avenue, LKS 5045, Cleveland, OH 44106, USA. E-mail: qing.zheng@case.edu

4These authors contributed equally to this work.

5Current address: Department of Otolaryngology and HNS, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853 China.

Received 4 November 2009; Revised 4 June 2010; Accepted 14 June 2010; Published online 20 July 2010.
Top of page
Abstract

We report a novel mutation (erlong, erl) of the cadherin 23 (Cdh23) gene in a mouse model for DFNB12 characterized by progressive hearing loss beginning from postnatal day 27 (P27). Genetic and sequencing analysis revealed a 208?T >C transition causing an amino-acid substitution (70S–P). Caspase expression was upregulated in mutant inner ears. Hearing was preserved (up to 35-dB improvement) in pan-caspase inhibitor Z-VAD-FMK-treated mutants compared with untreated mutants (P<0.05). Outer hair cell (OHC) loss in the cochleae of Z-VAD-FMK-treated mutants was significantly reduced compared with those of untreated mice. Thus, the erl mutation can lead to hearing loss through apoptosis. This is the first genetic mouse model of hearing loss shown to respond to otoprotective drug therapy. The short interval from initial hearing loss to deafness (P27–P90) makes this model ideal for screening and validating otoprotective drugs.

Kiwiagogoland

Hello y'all Hope everything is good with all of you and the weather is wonderful and not raining as it was here. Both Ed and I are loving New Zealand but we should probably work chronologically and take you back to our last evening and full day in Sydney which now seems like a lifetime ago. So we did go to the posh Indian I mentioned in the former blog and it did not dissapoint first of all

Alone but not alone…

Jeee What a lifeJust spoke to the ex boyfriend for some explanations I did not want to hear just broke up with the boyfriend I didn't know I had oups do I need to put a breakNO This is great When you live to go to some places you thinks all is going to stay behind. But is does not And the older you get the worst and worst it is I mean changes are usually for good well my horoscope

Happy reading

he first thing I want to emphasize thatis that reading should be enjoyable. Although sr there are many books that we all have to drive or to take examinations orinformation from which it is impossible toextract enjoyment. We aro to read theeducation and the best we can hope thatis that we need that will allow us toget through them without todium. These books read wo pleased with resignation

Flores

9th day FloresI'm not particularly happy about domestic flights had a few rough one's in Ethiopia and have developed a bit of a fear for them this one however was smooth as I arrived in Flores at kimodo airport in the small coastal town of Labuan Bajo with the plan of getting an official taxi one with a metre. There were no official taxi's to be seen however.I got in any old taxi another c

bye bye Paris Hello Prades

We leave Paris for Prades France today. It has been a wonderful time here. We ate more Italian food than french but that is what happens when you travel with kids or at least our kids. We did have some nice french wine to make up for the lack of french cusine. Jeff and I are depending on Cindy and Russells hospitality to get our fill of french food. I will send pictures and some fun updates

Sick sweat storms and sleeplessness

I have to write this entry more for my own memory than anything else. The journey to Koh Chang was something else and I don't want to forget all that we went through to get to this island known to most as a tropical oasis but to us has been something quite different but that is another entry altogetherWe left Pai at 2.30pm on Wednesday afternoon. We had bought a direct ticket to Koh Chang for 1

Is Dharamsala really the answer to Tibetans troubles

I really am living her life now. For those who donrsquot know who Irsquom talking about her name is Lhamo Tso. She is 37 and has been through more than we can imagine. Her husband is Dhondup Wangchen somewhat of a hero in Tibet due to the legendary documentary he made documenting the feelings of Tibetans about various things in 2008. As a consequence of this he was imprisoned for 6 years. He

Tour Anchorage

It is actually a warm and sunny day We wore Seth and Vivian out so they rested and played with Rowanquietly and didnrsquot go anywhere. The rest of us went downtown in Anchorage. First we went to the Ulu Factory. An ulu is a woman's knife that is very utilitarian and is now used by the rest of us to cut up food. Outside they were selling reindeer hotdogs so we each tried them. Yum Then we w

No one prepared me for this…

So.... I did get slightly sunburned yesterday at the beach. One of those sunburns that doesn't peel and goes away within 23 days so I'm ok with that. What I am NOT ok with is the rooster that is probably 20 yards outside my balcony window. The rooster that must think it is sunrise at 1am 4am 730am and currently right now at 821am. This is not a joke. That thing cockadoodledoos wayyyyyyyy to

Whittier

Another day of adventure. We decided to drive to Whittier which is a port town. We drove along Turnagain Arm which is an arm of the Cook Inlet which comes out of the Gulf of Alaska. It has some of the highest tides in the country at 28 feet and a tide called a bore tide. The ldquoArmrdquo is quite shallow. At low tide it is mostly a mudflat but beluga whales are said to frequent it. With o

i’m on a roll

Hi EveryoneDidn't think I'd be able to update so often but I'm up bright and early some things never change even in completely different time zones...We got to do some touristy stuff around Cape Town yesterday and I really wanted to share some pics so let's see how this uploading thing goes.....Off to the townships today work starts tomorrow. Hope everyone is good back home

Arbeit in NZ

So meine Liebenzwischen meinem letzten Bericht und dem von jetzt ist nicht viel passiert also versuche ich ihn kurz zu halten. Ein paar Highlights gab es allerdings dochIch habe jetzt den Job gewechselt weil es hier mehr Geld gibt und arbeite jetzt auf Experimentierfeldern fuer Kiwis. Wir saegen alte Weinreben ab und stecken neue kleine Kiwipfeiler in die Staemme tapen das Ganze und bestreich

Et gensyn med Fiji i Seattle

S efter 14 dage uden moderne bekvemmeligheder som aircondition internet og cable tv var det dejligt at kunne tjekke mailen se nyheder og lave popcorn igen. Vi var begge s fyldte ovenp alle de oplevelser vi havde i Yellowstone og Grand Teton at det eneste vi egentligt havde lyst til var bare at trkke stikket ud nogle dage og lave ingenting. Vi indlogerede os p en rigtig dejlig campground

Waffles and wall art

KyleBeef beans rice plantain salad with a soup. Chicken beans rice plantain salad with a soup. Beef beans rice plantain salad with a soup... The monotony of a menu corriente was only one of the reasons why we were looking forward to getting away from the village life and back to the big smoke. Normally I don't like the hustle and bustle of cities but after three weeks of tiny fishing v

Glacier Walk

One of the exciting things about Alaska is the glaciers. Janetrsquos number one hope was to walk on a glacier during her Alaskan vacation. The Matanuska Glacier that we saw on our way into Anchorage has a walking trail access to the glacier. We piled everybody into the pickup again and stopped to see Uncle Dick on the way out of town. Rowan was too shy to talk but after we got back in the truc

Nadi Fiji

I got into Fiji 3 days ago and I'm leaving for Vanuatu tomorrow morning. So Nadi...it's what I envision Cuba looking like 20 years ago it's pretty rundown. When the car picked me up from the airport all I could think was I hope the hostel isn't in downtown Nadi. I new it was on a beach but Nadi is on the water too. Anyways the hostel Smugglers Cove is on the edge of Nadi and has it's own

El Salvador LA Camp Day 1

Sunday 1 AugustWe awaken at 6am or so without an alarm clock having slept quite well after our long day of travel. By 7am we were having a delicious breakfast at our hotel including not only excellent local coffee but scrambed eggs with salsa ranchero pancakes fresh fruit Cantaloupe Mango and watermelon and believe it or not refried black beans. Actually the beans went quite well w