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Phenotypes Associated with This Genotype
Genotype
MGI:3777760
Allelic
Composition
Naglutm1Efn/Naglutm1Efn
Genetic
Background
involves: 129S/SvEv * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Naglutm1Efn mutation (1 available); any Naglu mutation (22 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Middle ear abnormalities in Naglutm1Efn/Naglutm1Efn mice at 30 weeks of age

mortality/aging
• average age of death is 315-360 days

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

behavior/neurological
• percentage of daily activity which occurs during the light portion of the LD cycle is increased in mutants
• 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
• rotarod testing shows a progressive inability of older, but not younger, mutants to coordinate movement in a rocking paradigm

nervous system
• complete loss of hair cells in the lower base coincides with degeneration of the organ of Corti
• the suprachiasmatic nucleus (SCN) shows a large number of pyknotic cells with condensed nuclei and cytoplasms and distended lysosomes
• age dependent loss of Purkinje cells
• diffuse decrease in cerebellar Purkinje neuronal counts at the vermis in older, but not younger, mutants
• progressive shortening of the outer segments

hearing/vestibular/ear
• inflammatory cells are more likely to appear in the perilymphatic scalae of mutants than wild-type and often show lysosomal storage
• lysosomal storage is seen in Reissner's membrane
• lysosomal storage in the organ of Corti occurs within outer sulcus cells of the lateral organ and pillar cells of the medial organ
• complete loss of hair cells in the lower base coincides with degeneration of the organ of Corti
• lysosomal storage is seen in the spiral ligament
• lysosomal storage is seen in the spiral limbus
• abnormal lysosomal storage in the crista ampullaris of the lateral semicircular canal
• the vestibular maculae and cristae show prominent lysosome storage in both supporting cells and hair cells and the dark cells of the cristae
• 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
• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells
• bone surface of the stapes is pitted, indicating abnormal bone remodeling
• increase in high frequency ABR thresholds is significantly greater in mutants up to 16 weeks than in controls
• auditory brainstem response (ABR) shows progressive hearing deficits
• middle ears at 30 weeks of age exhibit highly variable otitis media, with and without effusion

vision/eye
• aberrant lysosomal storage is seen in the inner retina
• progressive shortening of the outer segments
• localized disruption and inclusions in the retinal pigment epithelium
• progressive reduction of the outer nuclear layer
• lysosomal storage in the sclera
• ERG shows a progressive decrease in the amplitude of the dark-adapted b-wave response
• 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
• middle ears at 30 weeks of age exhibit highly variable otitis media, with and without effusion

craniofacial
• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells
• bone surface of the stapes is pitted, indicating abnormal bone remodeling

pigmentation
• localized disruption and inclusions in the retinal pigment epithelium

skeleton
• thickened mucosal layer on stapes and malleus at 30 weeks of age with hyperplasia of mucosal cells
• bone surface of the stapes is pitted, indicating abnormal bone remodeling
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
05/19/2020
MGI 6.15
The Jackson Laboratory