Phenotypes Associated with This Genotype

Genotype
MGI:3711773

• Allelic Composition: Bmp4^tm1Blh/Bmp4⁺
• Genetic Background: B6.129S2-Bmp4^tm1Blh

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

Anterior eye segment abnormalities in Bmp4^tm1Blh/Bmp4⁺ mice

mortality/aging

perinatal lethality, incomplete penetrance ( J:42445 )

• less than half as many heterozygotes are born as expected

vision/eye

abnormal eye morphology ( J:82877 )

• Background Sensitivity: mutants on a C57BL/6J background exhibit variable anterior and posterior segment abnormalities that are reduced on a mixed C3Hf/HeA and C57BL/LiA background and are rarely seen in mutants on CAST/Ei, 129S6/SvEvTac, or BALB/cJ background

abnormal anterior eye segment morphology ( J:82877 )

• variable anterior segment abnormalities in mutants 3-5 months of age

abnormal iridocorneal angle ( J:82877 )

• abnormal in most eyes

abnormal canal of Schlemm morphology ( J:82877 )

• small or absent

absent Schlemm's canal ( J:82877 )

• small or absent

abnormal line of Schwalbe morphology ( J:82877 )

• displaced Schwalbe's line

absent trabecular meshwork ( J:82877 )

• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development

hypoplastic trabecular meshwork ( J:82877 )

• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development

abnormal placement of pupils ( J:82877 )

• pupils are often eccentrically located

irregularly shaped pupil ( J:82877 )

iris hypoplasia ( J:82877 )

• iris is generally normal, however in some eyes, the iris is hypoplastic and malformed; occasionally the malformation is extensive involving both iris and ciliary body

abnormal cornea morphology ( J:82877 )

• extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles

anterior iris synechia ( J:82877 )

• abnormal iridocorneal attachments (anterior synechiae) of variable extent

decreased cornea thickness ( J:82877 )

• peripheral cornea is often thinner with neovascularization

cornea opacity ( J:82877 )

• some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze

cataract ( J:82877 )

anterior cortical cataract ( J:82877 )

• anterior subcapsular and cortical contaracts occur in most mutants

anterior subcapsular cataract ( J:82877 )

• anterior subcapsular and cortical contaracts occur in most mutants

abnormal eye size ( J:42445 )

microphthalmia ( J:42445 )

• frequency increased 3 fold

abnormal posterior eye segment morphology ( J:82877 )

• variable posterior eye segment abnormalities

abnormal optic nerve morphology ( J:82877 )

• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue

abnormal optic disk morphology ( J:82877 )

• abnormalities of the optic nerve head are frequently observed

absent optic nerve ( J:82877 )

• the optic nerve is sometimes absent

abnormal retina morphology ( J:82877 )

abnormal retina blood vessel pattern ( J:82877 )

• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type

thin retina ganglion layer ( J:82877 )

• retinal ganglion cell layer on average contains about 50% the normal number of cells

thin retina inner nuclear layer ( J:82877 )

abnormal retina photoreceptor layer morphology ( J:82877 )

• photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation

retina detachment ( J:82877 )

• about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age

abnormal vitreous body morphology ( J:82877 )

• dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels

persistence of hyaloid vascular system ( J:82877 )

• abnormal persistence of the anterior hyaloid vessels

• posterior hyaloid vessels persist throughout the 17 month period studied and increase in number and size beyond that normally seen at birth

increased opacity of vitreous body ( J:82877 )

• irregular white patches in the vitreous and dense vitreous haze in the majority of eyes

anophthalmia ( J:42445 )

• frequency increased 3 fold

abnormal eye electrophysiology ( J:82877 )

• in some eyes, both a- and b-wave amplitude are reduced, due in part to poor pupillary dilation, with preferential loss of b-wave relative to a-wave

ocular hypertension ( J:82877 )

• mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure

hearing/vestibular/ear

abnormal vestibulocollic reflex ( J:118380 )

• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction

• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1

• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function

abnormal organ of Corti morphology ( J:118380 )

• 2 of 4 circler and 2 of 4 non-circler heterozygotes show reduced neuronal processes in the organ of Corti

• in contrast, the saccule, utricle and ampullae of heterozygotes show normal numbers of neuronal processes

decreased vestibular hair cell stereocilia number ( J:118380 )

• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia

• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle

• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues

increased or absent threshold for auditory brainstem response ( J:118380 )

• most circling heterozygotes exhibit elevated ABR thresholds across all test frequencies (7 out of 11 mice at 6 kHz and 12 kHz; 8 out of 11 mice at 24 kHz)

• non-circlers display elevated ABR thresholds similar to those of circlers

impaired hearing ( J:118380 )

• both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing

nervous system

decreased vestibular hair cell stereocilia number ( J:118380 )

• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia

• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle

• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues

abnormal sensory neuron innervation pattern ( J:118380 )

• neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number

abnormal optic nerve morphology ( J:82877 )

• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue

abnormal optic disk morphology ( J:82877 )

• abnormalities of the optic nerve head are frequently observed

absent optic nerve ( J:82877 )

• the optic nerve is sometimes absent

behavior/neurological

abnormal vestibulocollic reflex ( J:118380 )

• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction

• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1

• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function

circling ( J:118380 )

• by 2 weeks of age, 10% of heterozygous pups display circling behavior

• 1 of 2 circlers spent 50% of the time circling in a clockwise direction, 17% in a counterclockwise direction and 33% not circling

• the second circler spent 65% of the time circling in a clockwise direction, 1% in a counterclockwise direction and 34% not circling

reproductive system

abnormal male reproductive system morphology ( J:42445 )

♂

abnormal prostate gland anterior lobe morphology ( J:42445 )

♂ • sometimes cystic

♂ • sometimes with abnormal lobulation

abnormal seminiferous tubule morphology ( J:42445 )

♂ • sometimes cystic

abnormal fertility/fecundity ( J:118380 )

reduced female fertility ( J:118380 )

♀ • female heterozygotes are poorer breeders relative to wild-type females

decreased litter size ( J:118380 )

• average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup

cardiovascular system

abnormal retina blood vessel pattern ( J:82877 )

• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type

renal/urinary system

kidney cyst ( J:42445 )

• single cystic kidney in about 12% of heterozygotes

• multiple cysts involving both tubules and glomeruli

hydronephrosis ( J:42445 )

• marked hydronephrosis in 12% of heterozygotes but ureter is undilated

kidney atrophy ( J:42445 )

• cortex of remaining kidney is atrophic

single kidney ( J:42445 )

• single cystic kidney in about 12% of heterozygotes

craniofacial

short frontal bone ( J:42445 )

• in about 12% of individuals

short nasal bone ( J:42445 )

• in about 12% of individuals

limbs/digits/tail

polydactyly ( J:42445 )

• 12% with unilateral anterior polydactyly involving the right hind limb only

skeleton

short frontal bone ( J:42445 )

• in about 12% of individuals

short nasal bone ( J:42445 )

• in about 12% of individuals

endocrine/exocrine glands

abnormal prostate gland anterior lobe morphology ( J:42445 )

♂ • sometimes cystic

♂ • sometimes with abnormal lobulation

abnormal seminiferous tubule morphology ( J:42445 )

♂ • sometimes cystic

growth/size/body

short nasal bone ( J:42445 )

• in about 12% of individuals

kidney cyst ( J:42445 )

• single cystic kidney in about 12% of heterozygotes

• multiple cysts involving both tubules and glomeruli

respiratory system

short nasal bone ( J:42445 )

• in about 12% of individuals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Axenfeld-Rieger syndrome type 3		DOID:0110122	OMIM:602482	J:82877