Phenotypes Associated with This Genotype

Genotype
MGI:5302243

• Allelic Composition: Tg(CMV-MYOC*Y437H)#Vcs/0
• Genetic Background: involves: C57BL/6J * SJL/J

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

vision/eye

abnormal eye morphology ( J:178254 )

• mutants develop glaucoma phenotypes including elevated intraocular pressure, retinal ganglion cell death, and axonal degeneration resembling primary open angle gluacoma patients

• the chemical chaperone, phenylbutyric acid, which reduces ER stress rescues the glaucoma phenotype

• however, the iridocorneal angle is open and mutants do not exhibit abnormalities of the iris, ciliary body, or cornea

retina ganglion cell degeneration ( J:178254 )

• progressive structural and functional loss of retinal ganglion cells, with a loss of 17.6% by 3-5 months of age and 30% by 12-14 months of age

optic nerve degeneration ( J:178254 )

• mutants lose 20.8% of optic nerve axons by 4-5 months of age and 36.1% by 12-14% months of age

abnormal trabecular meshwork morphology ( J:178254 )

• 12 month old mutants exhibit loss of trabecular meshwork cells

• mutants show rough endoplasmic reticulum distention in trabecular meshwork cells compared to wild-type

abnormal eye electrophysiology ( J:178254 )

• mutants exhibit a 38.7% reduction in pattern electroretinography (PERG) amplitude at 3-5 months of age and 63.7% reduction at 12-16 months compared to wild-type mice

ocular hypertension ( J:178254 )

• starting at 3 months of age, mutants show an elevation of intraocular pressure (IOP)

• mutants exhibit highest IOP during the night (20.3 mmHg vs. 14.1 mmHg in wild-type)

nervous system

neuron degeneration ( J:178254 )

• progressive neuronal degeneration

retina ganglion cell degeneration ( J:178254 )

• progressive structural and functional loss of retinal ganglion cells, with a loss of 17.6% by 3-5 months of age and 30% by 12-14 months of age

optic nerve degeneration ( J:178254 )

• mutants lose 20.8% of optic nerve axons by 4-5 months of age and 36.1% by 12-14% months of age

axon degeneration ( J:178254 )

• mutants lose 20.8% of optic nerve axons by 4-5 months of age and 36.1% by 12-14% months of age

cellular

abnormal endoplasmic reticulum morphology ( J:178254 )

• mutants show rough endoplasmic reticulum distention in trabecular meshwork cells compared to wild-type

increased endoplasmic reticulum stress ( J:178254 )

• mutants exhibit induction of endoplasmic reticulum stress

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary open angle glaucoma		DOID:1070	OMIM:137760	J:178254