Phenotypes Associated with This Genotype

Genotype
MGI:8172775

• Allelic Composition: Timm8a1^em1Yfhu/Y
• Genetic Background: C57BL/6J-Timm8a1^em1Yfhu

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

growth/size/body

decreased body size ( J:346289 )

♂ • 12-week-old mice are smaller than wild-type mice and have smaller organs except for the brain

slow postnatal weight gain ( J:346289 )

♂ • mice gain less weight after 2 weeks of age

behavior/neurological

impaired spatial learning ( J:346289 )

♂ • mice show impaired learning ability in the Morris water maze at 40 weeks of age, taking more time to reach the submerged platform over the training trials, in particular on days 1 and 4

abnormal long-term spatial reference memory ( J:346289 )

♂ • in the probe trial test of the Morris water maze, mice spend less time in the target quadrant and cross less around the target quadrant

impaired coordination ( J:346289 )

♂ • 10-week-old mice fall more times from the rotarod than wild-type mice, but no difference in fall times is seen at 24 and 34 weeks of age

♂ • in the balance beam test, the number of hind limb slips crossing the beam varies at difference ages, with no differences at 10 and 34 weeks, but increased limb slips at 24 weeks of age

♂ • however, no difference in fall times on the balance beam are seen at 24 and 34 weeks of age and grip strength is normal

increased thermal nociceptive threshold ( J:346289 )

♂ • in the hot plate test, mice show an increase in the latency in response to heat pain at 10 weeks of age, but not at 24 or 34 weeks of age, indicating impaired pain perception at an early age but not as mice grow older

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:346289 )

♂ • the auditory brain stem response (ABR) thresholds to click 8, 16, and 32 kHz pure-tone stimuli are elevated by approximately 17, 20, 28, and 24 dB sound pressure level in 4 to 5-week-old mice, respectively

impaired hearing ( J:346289 )

♂ • mice exhibit elevated hearing threshold in early age, indicating impaired hearing at a young age

nervous system

nervous system phenotype ( J:346289 )

♂N • no differences are seen in the cortex, hippocampus or cerebellum morphology

cellular

abnormal mitochondrial morphology ( J:346289 )

♂ • dramatic changes in mitochondrial morphology and cristae organization are seen in the primary motor cortex, primary visual cortex, primary auditory cortex, cerebellar lobules, and quadriceps femoris muscle at 24 weeks of age

♂ • the primary auditory cortex shows even more severe mitochondrial morphology with many mitochondria having multilamellar appearance and vacuolation

♂ • fragmented mitochondria are seen within autosomes in the primary motor cortex and primary visual cortex

♂ • however, the levels of OXPHOS and activity of respiratory chain complexes I-IV are unchanged

abnormal mitochondrial crista morphology ( J:346289 )

♂ • swollen mitochondria with broken cristae are seen in the primary motor cortex, primary visual cortex, and quadriceps femoris

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
deafness-dystonia-optic neuronopathy syndrome		DOID:0050757	OMIM:304700	J:346289