Phenotypes associated with this allele

• Allele Symbol: Fras1^bl
• Allele Name: blebbed
• Allele ID: MGI:1856691
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fras1^bl/Fras1^bl	involves: 101/H * C3H/HeH	MGI:2657302
ht2	Fras1^bl/Fras1^tm1.2Pjsc	involves: 101/H * C3H/HeH * C57BL/6 * FVB/N * SJL	MGI:5449398
cx3	Fras1^bl/Fras1^bl Frem2^my-Ucl/Frem2^my-Ucl	involves: 101/H * C3H/HeH * NMRI	MGI:3579981

Genotype
MGI:2657302

hm1

• Allelic Composition: Fras1^bl/Fras1^bl
• Genetic Background: involves: 101/H * C3H/HeH

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:83745 )

• most homozygotes die before birth

• however, a few reach adulthood with no signs of skin blistering

limbs/digits/tail

syndactyly ( J:83745 )

• adult homozygotes exhibit distal limb defects, such as syndactyly of the hindlimbs

clubfoot ( J:13501 , J:83745 )

• homozygotes may exhibit clubbed feet or hands (J:13501)

renal/urinary system

kidney cyst ( J:83745 )

• 2 of 146 live-born survivors display grossly cystic kidneys

abnormal kidney development ( J:83745 )

• at E11.5-E15.5, homozygotes show a range of defects in metanephric kidney development, followed by degeneration of early metanephric rudiments

• however, 20% of homozygous mutant embryos display a relatively normal metanephric development, including formation of glomeruli by E15.5

abnormal metanephric mesenchyme morphology ( J:83745 )

• by E13.5-E14.5, the metanephric mesenchyme is poorly differentiated with many cells containing pyknotic nuclei suggestive of apoptosis

increased metanephric mesenchyme apoptosis ( J:83745 )

• by E13.5-E14.5, many cells contain pyknotic nuclei suggesting apoptosis

abnormal metanephros morphology ( J:83745 )

• at E11.5-E15.5, some homozygotes display small and pooorly differentiated metanephroi, followed by degeneration of early metanephric rudiments

delayed kidney development ( J:83745 )

• by E13.5-E14.5, mutant kidneys appear developmentally delayed and are much smaller than those of wild-type mice

small kidney ( J:83745 )

• at E13.5-E14.5

absent kidney ( J:13501 , J:83745 )

• homozygotes may lack one or both kidneys (J:13501)

single kidney ( J:13501 , J:83745 )

• homozygotes may exhibit only one kidney (J:13501)

• 20 of 146 live-born survivors display complete unilateral renal agenesis (J:83745)

abnormal ureteric bud morphology ( J:83745 )

• at E11.5-E12.5, homozygous mutant embryos exhibit a dilated uteric bud

impaired branching involved in ureteric bud morphogenesis ( J:83745 )

• at E11.5-E12.5, homozygous mutant embryos display reduced ureteric bud branching relative to wild-type embryos

vision/eye

microphthalmia ( J:13501 )

• homozygotes display reduced eyes

cryptophthalmos ( J:83745 )

• adult homozygotes display cryptophthalmos

integument

abnormal hair growth ( J:13501 )

• homozygotes often display abnormal hair development between the eyes

bleb ( J:13501 )

• blebs are still visible at birth

fetal bleb ( J:83745 )

• at E14.5, homozygotes display prominent blebs over the rump and smaller blebs over the head and forelimb

• however, homozygotes that survive and are live-born show no signs of skin blistering

cellular

increased metanephric mesenchyme apoptosis ( J:83745 )

• by E13.5-E14.5, many cells contain pyknotic nuclei suggesting apoptosis

abnormal basement membrane morphology ( J:83745 )

• separation of the basement membrane from the dermis occurs at ~E11.5, prior to the development of overt blebs

embryo

increased metanephric mesenchyme apoptosis ( J:83745 )

• by E13.5-E14.5, many cells contain pyknotic nuclei suggesting apoptosis

growth/size/body

kidney cyst ( J:83745 )

• 2 of 146 live-born survivors display grossly cystic kidneys

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
clubfoot		DOID:11836	OMIM:119800	J:83745
Fraser syndrome		DOID:0090001	OMIM:PS219000	J:83745

Genotype
MGI:5449398

ht2

• Allelic Composition: Fras1^bl/Fras1^tm1.2Pjsc
• Genetic Background: involves: 101/H * C3H/HeH * C57BL/6 * FVB/N * SJL

Renal glomerulus abnormalities in Fras1^bl/Fras1^tm1.2Pjsc mice

renal/urinary system

renal/urinary system phenotype ( J:190659 )

N • mice exhibit normal kidney size and shape

abnormal glomerular capsule space morphology ( J:190659 )

• contains red cells unlike in control mice

abnormal renal glomerulus morphology ( J:190659 )

• in 4 of 7 sets of kidneys, with some that are smaller and less mature than in control mice

abnormal glomerular capillary morphology ( J:190659 )

• smaller capillary loops than in control mice

abnormal glomerular mesangium morphology ( J:190659 )

• more prominent than in control mice

cortical renal glomerulopathies ( J:190659 )

• variable in severity and extent

glomerulosclerosis ( J:190659 )

• in 10% to 20%

integument

integument phenotype ( J:190659 )

N • mice do not exhibit skin lesions

cardiovascular system

abnormal glomerular capillary morphology ( J:190659 )

• smaller capillary loops than in control mice

Genotype
MGI:3579981

cx3

• Allelic Composition: Fras1^bl/Fras1^bl; Frem2^my-Ucl/Frem2^my-Ucl
• Genetic Background: involves: 101/H * C3H/HeH * NMRI

mortality/aging

prenatal lethality, incomplete penetrance ( J:98344 )

• approximately 50% homozygotes died before birth

limbs/digits/tail

syndactyly ( J:98344 )

• cutaneous syndactyly and occasional bony syndactyly and polydactyly

vision/eye

cryptophthalmos ( J:98344 )

renal/urinary system

kidney cortex cyst ( J:98344 )

• adult mice (20 weeks) developed renal cysts

• increased proliferation and apoptosis are seen in these cysts

integument

fetal bleb ( J:98344 )

• shows epithelial "blebbing" during embryogenesis starting at E11.5

growth/size/body

kidney cortex cyst ( J:98344 )

• adult mice (20 weeks) developed renal cysts

• increased proliferation and apoptosis are seen in these cysts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fraser syndrome		DOID:0090001	OMIM:PS219000	J:98344