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 "hearing impairment" symptom

22q11.2 deletion syndrome

achondroplasia

benign recurrent intrahepatic cholestasis

canavan disease

congenital diaphragmatic hernia

dentinogenesis imperfecta

hirschsprung disease

kabuki syndrome

kallmann syndrome

monosomy 21

oligodontia

pendred syndrome

zellweger syndrome

This symptom has already been validated