Mouse Genome Informatics
hm
    Kcnq1tm1Apf/Kcnq1tm1Apf
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Cochlear abnormalities in Kcnq1tm1Apf/Kcnq1tm1Apf mice

behavior/neurological
• noticeable by 4 weeks of age (J:66428)
• exhibit repetitive wobbling behavior that is noticeable by 4 weeks of age
• nodding is noticeable by 4 weeks of age (J:66428)
• noticeable by 4 weeks of age (J:66428)

hearing/vestibular/ear
• Reissner membrane is collapsed onto the tectorial membrane (J:66428)
• a denuded basilar membrane forms fibrous adhesions with the tectorial membrane and collapsed Reissner membrane
• 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)
• 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)
• degeneration is more severe at the basal end (J:66428)
• 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
• 42 to 45% reduction in the total volume of mutant stria vascularis relative to wild-type mice
• the tectorial membrane shows increased density and thickness, esp. in the apical and middle turns, and is absent in the basal turn
• 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)
• reduction in the volume of the endolymphatic compartment of the semicircular canal, associated with contraction and fibrosis of the membranous lining
• cystic collection of granular debris between adhesions of the outer membrane and the neuroepitheliun of the crista ampullaris
• reduction in the volume of the endolymphatic compartment of the vestibule, associated with contraction and fibrosis of the membranous lining
• the saccular macula lacks hair cells
• complete loss of sterocilia in the saccular maculae
• instead, a flat epithelium is found on the surface of the neuroepithelium
• 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 maculae are only modestly degenerated
• otoliths lack a homogeneous appearance and resemble stellate-shaped aggregates or a continuous solid mass
• 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)
• 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)
• congenital deafness

digestive/alimentary system
• 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
• isthmic regions of the gastric glands are dilated and appear populated by mucin-secreting cells and vacuolated parietal cells
• intrinsic factor-expressing chief cells appear smaller and are decreased in number
• parietal cells are decreased in number
• expansion of mucous neck cells
• mucosal hyperplasia accounts for the increase in gastric wall thickness
• 3-fold enlargement of the stomach
• gastric lumen pH 6-7 vs. pH 1-2 in wild-type

cardiovascular system
N
• normal cardiac electrophysiology (J:66428)

nervous system
• 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)
• the saccular macula lacks hair cells
• complete loss of sterocilia in the saccular maculae
• instead, a flat epithelium is found on the surface of the neuroepithelium
• homozygotes exhibit 45% and 48% fewer spinal ganglion cells relative to wild-type and heterozygous mice, respectively
• SGN degeneration occurs in all turns but is most severe in the middle and apical regions

homeostasis/metabolism
• elevation in serum gastrin levels

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Beckwith-Wiedemann Syndrome; BWS 130650 J:66428
Jervell and Lange-Nielsen Syndrome 1; JLNS1 220400 J:110797