Phenotypes Associated with This Genotype

Genotype
MGI:3809245

• Allelic Composition: Tg(Gfap-GFAP*R239H)60TMIke/0
• Genetic Background: involves: C57BL/6J

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

nervous system

nervous system phenotype ( J:139349 )

N • unlike patients with Alexander disease, megalencephaly is not detected

increased susceptibility to pharmacologically induced seizures ( J:139349 )

• increased frequency of severe convulsions and mortality following treatment with 20 mg kainate/kg compared to controls

• however sensitivity to pentylenetetrazole pilocarpine, or 4-aminopyridine induced seizures is similar to controls

cochlear hair cell degeneration ( J:138318 )

• following noise exposure, cochlear hair cell loss and degeneration is increased compared to controls

abnormal astrocyte morphology ( J:139349 )

• develop Rosenthal fibers in areas of the brain where GFAP aggregates are detected, such as the hippocampus

abnormal cochlear nerve morphology ( J:138318 )

• GFAP aggregates are present in the cochlear nerve

hearing/vestibular/ear

cochlear hair cell degeneration ( J:138318 )

• following noise exposure, cochlear hair cell loss and degeneration is increased compared to controls

increased susceptibility to noise-induced hearing loss ( J:138318 )

• more pronounced hearing loss at 4kHz is seen in 5 week old mutants at 1 and 4 weeks after noise exposure

• following noise exposure, in response to click stimulus ABR peaks disappear from wave I and changes in the intensity-latency function indicate cochlear damage

behavior/neurological

behavior/neurological phenotype ( J:139349 )

N • unlike patients with Alexander disease, spontaneous convulsions are not observed

increased susceptibility to pharmacologically induced seizures ( J:139349 )

• increased frequency of severe convulsions and mortality following treatment with 20 mg kainate/kg compared to controls

• however sensitivity to pentylenetetrazole pilocarpine, or 4-aminopyridine induced seizures is similar to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alexander disease		DOID:4252	OMIM:203450	J:138318 , J:139349