Phenotypes Associated with This Genotype

Genotype
MGI:4365644

• Allelic Composition: Sh3pxd2b^nee/Sh3pxd2b^nee
• Genetic Background: B10.Cg-H2^h4 Sh3pxd2b^nee/GrsrJ

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

growth/size/body

short snout ( J:153369 )

• in all homozygotes

decreased body size ( J:153369 , J:262132 )

• at P17, homozygotes are ~15% smaller than wild-type controls (J:262132)

decreased body weight ( J:153369 )

• by 2 months of age homozygotes have a dramatically lower body weight than controls and do not continue to grow after 2 months of age

proportional dwarf ( J:153369 )

abnormal postnatal growth ( J:153369 )

• mice stop growing at 2 months of age

craniofacial

decreased cranium height ( J:153369 )

domed cranium ( J:153369 )

• in all homozygotes

short snout ( J:153369 )

• in all homozygotes

skeleton

decreased cranium height ( J:153369 )

domed cranium ( J:153369 )

• in all homozygotes

decreased bone mineral density ( J:153369 )

• DEXA analysis shows reduced bone mineral density in both males and females with females having even lower density than males

abnormal skeleton development ( J:153369 )

• proportionally smaller skeleton

reproductive system

infertility ( J:153369 )

• both female and male homozygotes are infertile

female infertility ( J:153369 )

♀ • although homozygous females are infertile, the ovaries function normally when transplanted into a normal host

male infertility ( J:153369 )

♂

vision/eye

hyphema ( J:262132 )

• mild hyphema is occasionally present in the anterior segment of the eye at 3 months of age

cornea vascularization ( J:262132 )

• corneal neovascularization is frequently observed by 10 months of age

eye inflammation ( J:262132 )

• only 2 of 19 eyes, containing hypermature cataracts, exhibit infiltration of leukocytes in the posterior eye segment

hypopyon ( J:262132 )

• occasional presence of large, inferiorly located pools of white cellular infiltrate (hypopyon) in the anterior segment of the eye at 3 months of age

optic nerve cupping ( J:262132 )

• severe optic nerve head excavation extending beyond the choroid at 3 months of age

optic nerve degeneration ( J:262132 )

• optic nerves show severe axon degeneration and areas of gliosis by 3 months of age

• although myelinated axons appear to be sparser at P17, no signs of damaged axons are detected at this age

optic nerve atrophy ( J:262132 )

• all eyes exhibit advanced optic nerve head atrophy by 3 months of age

• at 3 months of age, the cross-sectional area of the optic nerve is significantly reduced, consistent with a severe glaucomatous progression

abnormal iridocorneal angle ( J:262132 )

• abnormal development of the iridocorneal angle leading to severe ocular disease

absent Schlemm's canal ( J:262132 )

absent trabecular meshwork ( J:262132 )

irregularly shaped pupil ( J:262132 )

• occasionally misshapen pupils at P17

anterior iris synechia ( J:153369 , J:262132 )

• severe peripheral anterior synechiae are found in all homozygotes (J:153369)

• at P17, all eyes exhibit severe iridocorneal adhesions around the entire circumference of the eye that persist to 10 months of age (J:262132)

decreased cornea thickness ( J:262132 )

• significantly decreased central corneal thickness at 1 month of age

cornea opacity ( J:153369 , J:262132 )

• eyes are typically bulging with white corneal opacities, which are present to varying degree in all homozygotes (J:153369)

• focal corneal opacities are first observed at 1 month of age (J:262132)

• by 3 months of age, corneal opacities are observed in all homozygotes (J:262132)

abnormal eye anterior chamber morphology ( J:262132 )

• eyes exhibit anterior segment dysgenesis and early-onset glaucoma

abnormal aqueous humor ( J:262132 )

• severe iridocorneal adhesions presumably result in aqueous humor outflow blockage

increased eye anterior chamber depth ( J:153369 , J:262132 )

• the anterior chamber of the eye has a larger depth than normal (J:153369)

• enlarged anterior chamber depth at 3 months of age (J:262132)

enlarged eye anterior chamber ( J:153369 , J:262132 )

• anterior chamber enlargement is first observed at 1 month of age (J:262132)

• by 3 months of age, enlarged anterior chambers are observed in all homozygotes (J:262132)

cataract ( J:262132 )

• cataract formation is frequently observed at 3 months of age

• by 9-15 months of age, all eyes show some form of lens abnormality ranging from the presence of posteriorly located swollen cells (5 of 8 eyes) to hypermature cataracts (3 of 8 eyes)

mature cataract ( J:262132 )

• at 3 months of age, 7 of 19 eyes exhibit hypermature cataracts characterized by complete cortical and nuclear opacification with a wrinkled lens capsule

posterior subcapsular cataract ( J:262132 )

• at 3 months of age, 4 of 19 eyes exhibit a posterior subcapsular cataract

exophthalmos ( J:153369 )

abnormal retina morphology ( J:262132 )

• all retinas show indices of glaucomatous damage at 3 months of age

retina ganglion cell degeneration ( J:262132 )

• striking retinal ganglion cell loss, optic nerve head excavation, and axon loss at 3-4 months of age

abnormal retina nerve fiber layer morphology ( J:262132 )

• thinning of the retinal nerve fiber layer at 3 months of age

decreased total retina thickness ( J:262132 )

• panretinal thinning involving multiple layers is observed to various degrees with increasing age

ocular hypertension ( J:262132 )

• intraocular pressure (IOP) is significantly elevated (30.8 +/- 12.5 mmHg) at 3-4 months of age; similar IOP values are obtained at the earliest and latest time points tested (1.4 and 14.6 months of age)

nervous system

gliosis ( J:262132 )

• optic nerves show severe axon degeneration and areas of gliosis at 3 months of age

retina ganglion cell degeneration ( J:262132 )

• striking retinal ganglion cell loss, optic nerve head excavation, and axon loss at 3-4 months of age

optic nerve cupping ( J:262132 )

• severe optic nerve head excavation extending beyond the choroid at 3 months of age

optic nerve degeneration ( J:262132 )

• optic nerves show severe axon degeneration and areas of gliosis by 3 months of age

• although myelinated axons appear to be sparser at P17, no signs of damaged axons are detected at this age

optic nerve atrophy ( J:262132 )

• all eyes exhibit advanced optic nerve head atrophy by 3 months of age

• at 3 months of age, the cross-sectional area of the optic nerve is significantly reduced, consistent with a severe glaucomatous progression

cardiovascular system

hyphema ( J:262132 )

• mild hyphema is occasionally present in the anterior segment of the eye at 3 months of age

cornea vascularization ( J:262132 )

• corneal neovascularization is frequently observed by 10 months of age

adipose tissue

decreased white adipose tissue amount ( J:153369 )

• adult homozygotes have severely depleted visceral and subcutaneous white adipose tissue but normal brown adipose tissue, and this is less striking in young homozygotes

hearing/vestibular/ear

abnormal middle ear morphology ( J:153369 )

• serous fluid with diffuse neutrophils is found in the middle-ear cavities of all homozygotes and the surrounding epithelium is thickened by fibrous connective tissue and embedded neutrophils

increased or absent threshold for auditory brainstem response ( J:153369 )

• elevated thresholds to broad-band click and 8, 16, and 32 kHz pure tone stimuli at all ages tested, from 34 to 92 days of age

increased susceptibility to otitis media ( J:153369 )

immune system

increased susceptibility to otitis media ( J:153369 )

eye inflammation ( J:262132 )

• only 2 of 19 eyes, containing hypermature cataracts, exhibit infiltration of leukocytes in the posterior eye segment

hypopyon ( J:262132 )

• occasional presence of large, inferiorly located pools of white cellular infiltrate (hypopyon) in the anterior segment of the eye at 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glaucoma		DOID:1686		J:262132
otitis media		DOID:10754		J:153369