Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

[22q11.2 deletion syndrome]

22 q 11 .2 Deletion Syndrome (22 q 11 DS ) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes . This disorder is one of the most significant known cytogenetic risk factors for schizophrenia , and can also cause heart abnormalities , cognitive deficits , hearing difficulties , and a variety of other medical problems . The Df 1 /+ hemizygous knockout mouse , a model for human 22 q 11 DS , recapitulates many of the deficits observed in the human syndrome including heart defects , impaired memory , and abnormal auditory sensorimotor gating . Here we show that Df 1 /+ mice , like human 22 q 11 DS patients , have substantial rates of hearing loss arising from chronic middle ear infection . Auditory brainstem response (ABR ) measurements revealed significant elevation of click-response thresholds in 48 % of Df 1 /+ mice , often in only one ear . Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities , but frequent signs of otitis media (OM , chronic inflammation of the middle ear ), including excessive effusion and thickened mucosa . In mice for which both in vivo ABR thresholds and post mortem middle -ear histology were obtained , the severity of signs of OM correlated directly with the level of hearing impairment . These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22 q 11 DS could arise from abnormalities in auditory processing . Furthermore , the findings indicate that Df 1 /+ mice are an excellent model for increased risk of OM in human 22 q 11 DS patients . Given the frequently monaural nature of OM in Df 1 /+ mice , these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM .

Diseases
Validation

Diseases presenting "heart defects" symptom

22q11.2 deletion syndrome

cohen syndrome

hirschsprung disease

holt-oram syndrome

homocystinuria without methylmalonic aciduria

kabuki syndrome

monosomy 21

phenylketonuria

wolf-hirschhorn syndrome

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