Phenotypes Associated with This Genotype

Genotype
MGI:3777760

• Allelic Composition: Naglu^tm1Efn/Naglu^tm1Efn
• Genetic Background: involves: 129S/SvEv * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Middle ear abnormalities in Naglu^tm1Efn/Naglu^tm1Efn mice at 30 weeks of age

mortality/aging

premature death ( J:129390 )

• average age of death is 315-360 days

cellular

abnormal lysosome morphology ( J:129390 )

• mutants exhibit lysosomal distention in multiple tissues, including in the middle and inner ear, in the eye, and in the suprachiasmatic nucleus

behavior/neurological

impaired coordination ( J:129390 )

• rotarod testing shows a progressive inability of older, but not younger, mutants to coordinate movement in a rocking paradigm

abnormal circadian behavior ( J:129390 )

• percentage of daily activity which occurs during the light portion of the LD cycle is increased in mutants

delayed circadian behavior phase ( J:129390 )

• mutants differ from wild-type in their phase angle of entrainment (the time from the light offset to the onset of daily locomotor activity); mutants start their daily activity about 1 hour later than wild-type

nervous system

decreased cochlear hair cell number ( J:129390 )

• complete loss of hair cells in the lower base coincides with degeneration of the organ of Corti

abnormal suprachiasmatic nucleus morphology ( J:129390 )

• the suprachiasmatic nucleus (SCN) shows a large number of pyknotic cells with condensed nuclei and cytoplasms and distended lysosomes

Purkinje cell degeneration ( J:129390 )

• age dependent loss of Purkinje cells

decreased Purkinje cell number ( J:129390 )

• diffuse decrease in cerebellar Purkinje neuronal counts at the vermis in older, but not younger, mutants

short photoreceptor outer segment ( J:129390 )

• progressive shortening of the outer segments

hearing/vestibular/ear

abnormal inner ear morphology ( J:129390 )

abnormal cochlea morphology ( J:129390 )

• inflammatory cells are more likely to appear in the perilymphatic scalae of mutants than wild-type and often show lysosomal storage

abnormal Reissner membrane morphology ( J:129390 )

• lysosomal storage is seen in Reissner's membrane

abnormal organ of Corti morphology ( J:129390 )

• lysosomal storage in the organ of Corti occurs within outer sulcus cells of the lateral organ and pillar cells of the medial organ

decreased cochlear hair cell number ( J:129390 )

• complete loss of hair cells in the lower base coincides with degeneration of the organ of Corti

organ of Corti degeneration ( J:129390 )

abnormal spiral ligament morphology ( J:129390 )

• lysosomal storage is seen in the spiral ligament

abnormal spiral limbus morphology ( J:129390 )

• lysosomal storage is seen in the spiral limbus

abnormal crista ampullaris morphology ( J:129390 )

• abnormal lysosomal storage in the crista ampullaris of the lateral semicircular canal

abnormal inner ear vestibule morphology ( J:129390 )

• the vestibular maculae and cristae show prominent lysosome storage in both supporting cells and hair cells and the dark cells of the cristae

abnormal middle ear morphology ( J:129390 )

• middle ears at 30 weeks of age show lysosomal storage-related anomalies

• lysosomal storage is prominent in the mucosal lining and within osteocytes, chondrocytes, and inflammatory cells

abnormal middle ear ossicle morphology ( J:129390 )

• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells

abnormal stapes morphology ( J:129390 )

• bone surface of the stapes is pitted, indicating abnormal bone remodeling

increased or absent threshold for auditory brainstem response ( J:129390 )

• increase in high frequency ABR thresholds is significantly greater in mutants up to 16 weeks than in controls

conductive hearing loss ( J:129390 )

• auditory brainstem response (ABR) shows progressive hearing deficits

increased susceptibility to otitis media ( J:129390 )

• middle ears at 30 weeks of age exhibit highly variable otitis media, with and without effusion

vision/eye

abnormal retina morphology ( J:129390 )

• aberrant lysosomal storage is seen in the inner retina

short photoreceptor outer segment ( J:129390 )

• progressive shortening of the outer segments

abnormal retina pigment epithelium morphology ( J:129390 )

• localized disruption and inclusions in the retinal pigment epithelium

thin retina outer nuclear layer ( J:129390 )

• progressive reduction of the outer nuclear layer

abnormal sclera morphology ( J:129390 )

• lysosomal storage in the sclera

abnormal eye electrophysiology ( J:129390 )

• ERG shows a progressive decrease in the amplitude of the dark-adapted b-wave response

abnormal rod electrophysiology ( J:129390 )

• dark-adapted retinal response is depressed by 5 weeks and becomes progressively less sensitive with increasing age, indicating loss of rod function

• however, cone function appears normal

immune system

increased susceptibility to otitis media ( J:129390 )

• middle ears at 30 weeks of age exhibit highly variable otitis media, with and without effusion

craniofacial

abnormal middle ear ossicle morphology ( J:129390 )

• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells

abnormal stapes morphology ( J:129390 )

• bone surface of the stapes is pitted, indicating abnormal bone remodeling

pigmentation

abnormal retina pigment epithelium morphology ( J:129390 )

• localized disruption and inclusions in the retinal pigment epithelium

skeleton

abnormal middle ear ossicle morphology ( J:129390 )

• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells

abnormal stapes morphology ( J:129390 )

• bone surface of the stapes is pitted, indicating abnormal bone remodeling

abnormal spiral ligament morphology ( J:129390 )

• lysosomal storage is seen in the spiral ligament

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis III		DOID:12801	OMIM:252940	J:129390
otitis media		DOID:10754		J:129390