Phenotypes for Kcnq1 MGI:3623773 MGI Mouse

hyperactivity ( J:66428 , J:110797 )

• noticeable by 4 weeks of age (J:66428)

stereotypic behavior ( J:66428 )

• exhibit repetitive wobbling behavior that is noticeable by 4 weeks of age

head bobbing ( J:66428 , J:110797 )

• nodding is noticeable by 4 weeks of age (J:66428)

circling ( J:66428 , J:110797 )

• noticeable by 4 weeks of age (J:66428)

spinning ( J:110797 )

collapsed Reissner membrane ( J:66428 , J:110797 )

• Reissner membrane is collapsed onto the tectorial membrane (J:66428)

abnormal basilar membrane morphology ( J:110797 )

• a denuded basilar membrane forms fibrous adhesions with the tectorial membrane and collapsed Reissner membrane

absent cochlear hair cells ( J:66428 , J:110797 )

• hair cells of the organ of Corti are absent and are replaced by fibrous adhesions between the tectorial membrane and the basilar membrane (J:66428)

absent organ of Corti supporting cells ( J:66428 , J:110797 )

• supporting cells of the organ of Corti are absent and are replaced by fibrous adhesions between the tectorial membrane and the basilar membrane (J:66428)

organ of Corti degeneration ( J:66428 , J:110797 )

• degeneration is more severe at the basal end (J:66428)

abnormal stria vascularis morphology ( J:110797 )

• severe atrophy of the stria vascularis, esp. in the basal turn

• dense deposits of a hyaline material in apical turns, appearing to be an extension of the stria vascularis remnant

thin stria vascularis ( J:110797 )

• 42 to 45% reduction in the total volume of mutant stria vascularis relative to wild-type mice

abnormal tectorial membrane morphology ( J:110797 )

• the tectorial membrane shows increased density and thickness, esp. in the apical and middle turns, and is absent in the basal turn

small scala media ( J:66428 , J:110797 )

• severe contraction of the scala media, particularly in the basal end (J:66428)

• collapse of Reissner's membrane leads to a 64% and 73% reduction in the volume of scala media relative to wild-type and heterozygous mice, respectively (J:110797)

abnormal semicircular canal morphology ( J:66428 )

• reduction in the volume of the endolymphatic compartment of the semicircular canal, associated with contraction and fibrosis of the membranous lining

abnormal crista ampullaris morphology ( J:110797 )

• cystic collection of granular debris between adhesions of the outer membrane and the neuroepitheliun of the crista ampullaris

abnormal inner ear vestibule morphology ( J:66428 )

• reduction in the volume of the endolymphatic compartment of the vestibule, associated with contraction and fibrosis of the membranous lining

absent vestibular hair cells ( J:110797 )

• the saccular macula lacks hair cells

absent vestibular hair cell stereocilia ( J:110797 )

• complete loss of sterocilia in the saccular maculae

• instead, a flat epithelium is found on the surface of the neuroepithelium

abnormal vestibular labyrinth morphology ( J:110797 )

• the vestibular end organs show collapse of the membranous labyrinth

• the membranous walls of the saccule and utricle are collapsed onto the otolithic membrane

utricular macular degeneration ( J:110797 )

• utricular maculae are only modestly degenerated

abnormal otolith morphology ( J:110797 )

• otoliths lack a homogeneous appearance and resemble stellate-shaped aggregates or a continuous solid mass

detached otolithic membrane ( J:66428 , J:110797 )

• the otolithic membrane is separated from the neuroepithelium (J:66428)

• the otolithic membrane is separated from the neuroepithelium of the macula in both the utricle and the saccule (J:110797)

increased or absent threshold for auditory brainstem response ( J:110797 )

• homozygotes exhibit no detectable auditory brainstem responses (ABRs) to clicks presented at 90 db or higher

• in contrast, wild-type mice display ABR thresholds ranging from 41 to 65 dB SPL (J:66428)

deafness ( J:110797 )

• congenital deafness

abnormal gastric chief cell morphology ( J:66428 )

• intrinsic factor-expressing chief cells appear smaller and are decreased in number

abnormal gastric parietal cell morphology ( J:66428 )

• parietal cells are decreased in number

abnormal mucous neck cell morphology ( J:66428 )

• expansion of mucous neck cells

dilated gastric gland ( J:66428 )

• isthmic regions of the gastric glands are dilated and appear populated by mucin-secreting cells and vacuolated parietal cells

stomach mucosa hyperplasia ( J:66428 )

• antral and fundic mucosa show hyperplasia, with changes more striking in the fundus

• majority of fundic hyperplasia occurs in the middle (isthmic) portion of the mucosa and in the gastric neck (proliferative compartment)

• the proliferative compartment of the mucosa is expanded in both the antrum and fundus and is disorganized

• mucosal hyperplasia accounts for the increase in gastric wall thickness

increased stomach mucosa thickness ( J:66428 )

• mucosal hyperplasia accounts for the increase in gastric wall thickness

enlarged stomach ( J:66428 )

• 3-fold enlargement of the stomach

hypochlorhydria ( J:66428 )

increased stomach pH ( J:66428 )

• gastric lumen pH 6-7 vs. pH 1-2 in wild-type

cardiovascular system phenotype ( J:66428 )

N	• normal cardiac electrophysiology