All Phenotypes Fzd4<tm1Nat> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fzd4^tm1Nat/Fzd4^tm1Nat	involves: 129S1/Sv * 129X1/SvJ	MGI:4412191
hm2	Fzd4^tm1Nat/Fzd4^tm1Nat	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3622318
cn3	Fzd4^tm1Nat/Fzd4^tm1Nat Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?	involves: 129 * C57BL/6 * CBA	MGI:4412196
cn4	Fzd4^tm1Nat/Fzd4⁺ Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?	involves: 129 * C57BL/6 * CBA	MGI:4412195
cn5	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ	MGI:4948329
cn6	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(rx3-icre)1Mjam/?	involves: 129S1/Sv * 129X1/SvJ	MGI:4412190
cn7	Fzd4^tm1Nat/Fzd4^tm2.1Nat Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:4948328
cn8	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(Tek-cre)1Ywa/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4412188
cx9	Fzd4^tm1Nat/Fzd4^tm1Nat Fzd8^tm1Nat/Fzd8⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:4948327
cx10	Fzd4^tm1Nat/Fzd4^tm1Nat Fzd8^tm1Nat/Fzd8^tm1Nat	involves: 129S1/Sv * 129X1/SvJ	MGI:4948325

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm1Nat
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fzd4^tm1Nat mutation (1 available); any Fzd4 mutation (31 available)

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

vision/eye

impaired pupillary reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

abnormal retina vasculature morphology ( J:154020 )

• vascular development on the vitreal face of the retina is retarded

• retinal mural cells are thinner and lower in density than in controls

abnormal eye electrophysiology ( J:154020 )

• electroretinogram a wave is relatively normal

• electroretinogram b wave is markedly reduced

behavior/neurological

abnormal optokinetic reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

impaired pupillary reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

nervous system

abnormal brain vasculature morphology ( J:154020 )

• progressive reduction in vascular density in the cerebellum

• misshapen capillaries in the cerebellum

• endothelial projections into the capillary lumen in the cerebellum

• leakage of IgG into the cerebellum

• frequent cerebellar hemorrhage but not in cerebral cortex

abnormal cerebellum morphology ( J:154020 )

• cerebellar degeneration observed

cardiovascular system

abnormal brain vasculature morphology ( J:154020 )

• progressive reduction in vascular density in the cerebellum

• misshapen capillaries in the cerebellum

• endothelial projections into the capillary lumen in the cerebellum

• leakage of IgG into the cerebellum

• frequent cerebellar hemorrhage but not in cerebral cortex

abnormal retina vasculature morphology ( J:154020 )

• vascular development on the vitreal face of the retina is retarded

• retinal mural cells are thinner and lower in density than in controls

renal/urinary system

small kidney ( J:170839 )

• at E18.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
exudative vitreoretinopathy		DOID:0050535	OMIM:PS133780	J:158585

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

mortality/aging

premature death ( J:70078 )

• 50% die within the first 4-5 months of life

growth/size/body

enlarged esophagus ( J:70078 )

• progressive enlargement of the esophagus apparent at 8 days of age but not at birth

weight loss ( J:70078 )

• weight is normal during the first week after birth

• weight gain is slower from the second week on

behavior/neurological

absent startle reflex ( J:70078 )

• eventually absent

decreased startle reflex ( J:70078 )

• normal at 1-2 months of age but diminishing thereafter and eventually disappears

ataxia ( J:70078 )

• cerebellar ataxia possibly causing the observed abnormal gait

abnormal posture ( J:70078 )

• widened stance

hunched posture ( J:70078 )

abnormal gait ( J:70078 )

• minimal alternation between right and left side

• frequently fail to fully lift each foot between steps

short stride length ( J:70078 )

• in older animals

hearing/vestibular/ear

abnormal organ of Corti morphology ( J:107732 )

cochlear hair cell degeneration ( J:107732 )

• eventually the near complete loss of hair cells, first the outer hair cells and then the inner hair cells

cochlear inner hair cell degeneration ( J:107732 )

cochlear outer hair cell degeneration ( J:107732 )

abnormal stria vascularis morphology ( J:107732 )

abnormal stria vascularis vasculature morphology ( J:107732 )

• enlarged blood vessels in the stria vascularis

• no identifiable blood vessels at 11 months of age

stria vascularis degeneration ( J:107732 )

• almost completely degenerated by 11 months of age

increased or absent threshold for auditory brainstem response ( J:70078 )

• elevated auditory thresholds are observed; in one case, the auditory brainstem response threshold is at least 40 dB higher than the average control value of ~60 dB

impaired hearing ( J:70078 )

• hearing loss does not require loss of primary sensory cells, either the outer or inner hair cells

nervous system

cochlear hair cell degeneration ( J:107732 )

• eventually the near complete loss of hair cells, first the outer hair cells and then the inner hair cells

cochlear inner hair cell degeneration ( J:107732 )

cochlear outer hair cell degeneration ( J:107732 )

abnormal cerebellum morphology ( J:107732 )

• vasculature of the cerebellum is noticeably sparser than controls at 30 days of age and very sparse and irregular at 6 months

• progressive cerebellar degeneration starting around 3rd postnatal week

decreased Purkinje cell number ( J:70078 )

• dramatic loss of Purkinje cells and vacuolization

• apoptosis not observed in Purkinje cells but cells are lost progressively through adulthood

abnormal cerebellar granule layer morphology ( J:70078 )

• dramatic loss of granule cells and vacuolization

• massive apoptosis of granule cells starting between 14 and 19 days of age

• 50X more apoptosis in the cerebellum at 19 days of age

• apoptosis drops off greatly at 30 days of age

cerebellum hypoplasia ( J:70078 )

• hypocellular cerebellum but cerebellar architecture normal

abnormal astrocyte physiology ( J:70078 )

• abnormal astroglial activation in adults

cardiovascular system

abnormal retina vasculature morphology ( J:107732 )

• the two intraretinal capillary beds fail to develop

• major arteries and veins on the retina are enlarged and tortuous

• arteriolar arborization is diminished

• increased density of small vessels in nerve fiber layer

• many retinal blood vessels are fenestrated

abnormal stria vascularis vasculature morphology ( J:107732 )

• enlarged blood vessels in the stria vascularis

• no identifiable blood vessels at 11 months of age

abnormal vascular development ( J:115734 )

• female homozygotes display disrupted vascular development of the corpora luteum

• markers of vascular cell function are reduced in ovaries of mutant female mice following natural mating

decreased angiogenesis ( J:328283 )

• delayed superficial blood vessel growth in retina

• reduced vascular density in retina

hemorrhage ( J:107732 , J:328283 )

• small hemorrhages frequent in cerebellum (J:107732)

• extensive blood leakage in retina (J:328283)

retina hemorrhage ( J:107732 )

• small hemorrhages frequent in retina

vision/eye

abnormal retina vasculature morphology ( J:107732 )

• the two intraretinal capillary beds fail to develop

• major arteries and veins on the retina are enlarged and tortuous

• arteriolar arborization is diminished

• increased density of small vessels in nerve fiber layer

• many retinal blood vessels are fenestrated

retina hemorrhage ( J:107732 )

• small hemorrhages frequent in retina

abnormal retina development ( J:328283 )

• delayed superficial blood vessel growth

• reduced vascular density

• extensive blood leakage

persistence of hyaloid vascular system ( J:107732 )

• hyaloid blood vessels fail to regress or regression is delayed 1-2 weeks

digestive/alimentary system

abnormal esophagus morphology ( J:70078 )

• loss of skeletal muscle on lower 1/4 of esophagous to as much as the entire esophagus

• no motor end plates along the lower portion of the esophagus

abnormal esophageal squamous epithelium morphology ( J:70078 )

• desquamination of the esophageal epithelium

enlarged esophagus ( J:70078 )

• progressive enlargement of the esophagus apparent at 8 days of age but not at birth

abnormal digestion ( J:70078 )

• defective esophageal peristalsis

• defective function of the gastric sphincter

muscle

decreased skeletal muscle fiber diameter ( J:70078 )

• muscle fibers with smaller diameter but otherwise normal

pigmentation

diluted coat color ( J:70078 )

• light black or silver coat color

reproductive system

reproductive system phenotype ( J:115734 )

• adult female homozygotes exhibit normal mating behavior relative to wild-type and heterozygous littermates

• following superovulation, female homozygotes produce an equal number of fertilized oocytes as their wild-type and heterozygous littermates

• immature mutant ovaries show normal follicular development and normal responses to gonadotropin stimulation during development to the preovulatory stage

impaired luteal cell differentiation ( J:115734 )

• whereas luteal cells in day 5.5 pregnant wild-type ovaries display cellular hypertrophy, luteal cells in day 5.5 non-pregnant mutant ovaries appear disorganized and display a lower cytoplasmic to nuclear ratio

• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc

abnormal corpus luteum morphology ( J:115734 )

• at 8 weeks of age, corpora lutea are variably present or absent in ovaries of some female mutant mice

• analysis of mutant ovaries from timed mating pairs shows that by day 7.5 pc, corpora lutea are not discernible, indicating that formation of functional corpora lutea is impaired

• on day 1.5 pc, mutant corpora lutea exhibit a thick, dense collagen IV network that is significantly less filamentous and punctate than that observed in wild-type corpora lutea, suggesting that vessel arborization is reduced during luteinization

• on day 1.5 pc, mutant corpora lutea exhibit clear signs of apoptosis, as indicated by the presence of activated caspase 3

absent corpus luteum ( J:115734 )

• after natural mating, some female homozygotes exhibit absence of corpora lutea

impaired luteinization ( J:115734 )

• mutant ovaries collected at days 1.5, 5.5, and 7.5 pc display an altered histological appearance, reduced expression luteal cell-specific mRNAs, and distinct structural abnormalities within the vascular network, indicative of impaired luteal cell function

failure of embryo implantation ( J:115734 )

• analysis of ovaries from timed mating pairs indicates that female homozygotes exhibit no implantation sites on days 5.5 and 7.5 pc

female infertility ( J:115734 )

• when mated to wild-type males, female homozygotes fail to become pregnant and produce offspring

male infertility ( J:115734 )

• preliminary observations suggest that male homozygotes appear to be infertile

homeostasis/metabolism

decreased circulating progesterone level ( J:115734 )

• on day 1.5 post-coitum (pc), serum progesterone levels are reduced by 50% in female mutant mice relative to wild-type females, and decrease dramatically on days 5.5 and 7.5 pc with no evidence of implantation

• in contrast, no significant differences are observed in serum prolactin levels between female mutant and wild-type mice on day 5.5 pc

endocrine/exocrine glands

impaired luteal cell differentiation ( J:115734 )

• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc

abnormal corpus luteum morphology ( J:115734 )

• at 8 weeks of age, corpora lutea are variably present or absent in ovaries of some female mutant mice

• analysis of mutant ovaries from timed mating pairs shows that by day 7.5 pc, corpora lutea are not discernible, indicating that formation of functional corpora lutea is impaired

• on day 1.5 pc, mutant corpora lutea exhibit clear signs of apoptosis, as indicated by the presence of activated caspase 3

absent corpus luteum ( J:115734 )

• after natural mating, some female homozygotes exhibit absence of corpora lutea

integument

diluted coat color ( J:70078 )

• light black or silver coat color

cellular

impaired luteal cell differentiation ( J:115734 )

• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
exudative vitreoretinopathy	DOID:0050535	OMIM:PS133780	J:328283
Norrie disease	DOID:0060844	OMIM:310600	J:107732

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm1Nat Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?
Genetic Background	involves: 129 * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Edil3^{Tg(Sox2-cre)1Amc} mutation (5 available); any Edil3 mutation (43 available)
Fzd4^tm1Nat mutation (1 available); any Fzd4 mutation (31 available)
Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} mutation (1 available); any Igs1 mutation (10 available)

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

mortality/aging

mortality/aging ( J:154020 )

N	• Background Sensitivity: normal survival

growth/size/body

growth/size/body region phenotype ( J:154020 )

N	• Background Sensitivity: normal phenotype

cardiovascular system

cardiovascular system phenotype ( J:154020 )

N	• Background Sensitivity: normal phenotype

Allelic Composition	Fzd4^tm1Nat/Fzd4⁺ Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?
Genetic Background	involves: 129 * C57BL/6 * CBA

Find Mice

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

mortality/aging

embryonic lethality, incomplete penetrance ( J:154020 )

• Background Sensitivity: mid-gestational lethality but some survival to E18

growth/size/body

embryonic growth retardation ( J:154020 )

• Background Sensitivity: growth retardation moderated

cardiovascular system

abnormal descending aorta morphology ( J:154020 )

• Background Sensitivity: disruption less severe

abnormal angiogenesis ( J:154020 )

• Background Sensitivity: less severely disrupted

embryo

embryonic growth retardation ( J:154020 )

• Background Sensitivity: growth retardation moderated

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(Tek-cre)1Ywa/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fzd4^tm1Nat mutation (1 available); any Fzd4 mutation (31 available)
Fzd4^tm2.1Nat mutation (1 available); any Fzd4 mutation (31 available)
Tg(Tek-cre)1Ywa mutation (6 available)

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

renal/urinary system

renal/urinary system phenotype ( J:170839 )

N	• kidney size is normal

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(rx3-icre)1Mjam/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

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

vision/eye

abnormal eye electrophysiology ( J:154020 )

• electroretinogram a wave is relatively normal

• electroretinogram b wave is markedly reduced

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm2.1Nat Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

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

renal/urinary system

small kidney ( J:170839 )

• at E18.5 in mice treated with tamoxifen at E12.5 or E13.5

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm2.1Nat Tg(Tek-cre)1Ywa/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

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

vision/eye

impaired pupillary reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

abnormal retina vasculature morphology ( J:154020 )

• vascular development on the vitreal face of the retina is retarded

• intra retinal capillaries are completely absent

• vessels from the vitreal surface penetrate the retina and end in ball-like structures

• large vessels are dilated and artery to vein anastomoses develop

• incomplete recombination in retinas creates mosaics in which capillaries form in some region

• vessels from conditionally knocked out regions can integrate into wild type capillary beds

abnormal eye electrophysiology ( J:154020 )

• electroretinogram a wave is relatively normal

• electroretinogram b wave is markedly reduced

behavior/neurological

abnormal optokinetic reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

impaired pupillary reflex ( J:154020 )

• rod and cone signals are not transmitted effectively

nervous system

abnormal brain vasculature morphology ( J:154020 )

• leakage of IgG into the cerebellum

cardiovascular system

abnormal brain vasculature morphology ( J:154020 )

• leakage of IgG into the cerebellum

abnormal retina vasculature morphology ( J:154020 )

• vascular development on the vitreal face of the retina is retarded

• intra retinal capillaries are completely absent

• vessels from the vitreal surface penetrate the retina and end in ball-like structures

• large vessels are dilated and artery to vein anastomoses develop

• incomplete recombination in retinas creates mosaics in which capillaries form in some region

• vessels from conditionally knocked out regions can integrate into wild type capillary beds

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm1Nat Fzd8^tm1Nat/Fzd8⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fzd4^tm1Nat mutation (1 available); any Fzd4 mutation (31 available)
Fzd8^tm1Nat mutation (1 available); any Fzd8 mutation (33 available)

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

renal/urinary system

small kidney ( J:170839 )

• at E18.5

Allelic Composition	Fzd4^tm1Nat/Fzd4^tm1Nat Fzd8^tm1Nat/Fzd8^tm1Nat
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

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

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:170839 )

• all mice die between E18.5 and P14

renal/urinary system

abnormal kidney development ( J:170839 )

• at E15.5, proliferation of epithelial cells within ureteric buds is decreased 1.8-fold compared to in wild-type mice

• however, cell proliferation in the rest of the developing kidney is normal

small kidney ( J:170839 )

• at E18.5

impaired branching involved in ureteric bud morphogenesis ( J:170839 )

• at E12.5

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