Phenotypes associated with this allele

• Allele Symbol: Foxi1^tm1Sven
• Allele Name: targeted mutation 1, Sven Enerback
• Allele ID: MGI:2448634
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxi1^tm1Sven/Foxi1^tm1Sven	involves: 129S1/Sv * 129X1/SvJ	MGI:4366849
hm2	Foxi1^tm1Sven/Foxi1^tm1Sven	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2679654
hm3	Foxi1^tm1Sven/Foxi1^tm1Sven	involves: CD-1	MGI:3056282
ht4	Foxi1^tm1Sven/Foxi1^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2679655

Genotype
MGI:4366849

hm1

• Allelic Composition: Foxi1^tm1Sven/Foxi1^tm1Sven
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

reproductive system

reproductive system phenotype ( J:112876 )

N • male homozygotes display normal epididymal sperm counts and normal sperm motility relative to wild-type males

kinked sperm flagellum ( J:112876 )

♂ • male homozygotes show a significantly higher number of sperm with tail angulations than wild-type males

abnormal epididymis morphology ( J:112876 )

♂ • mutant epididymides exhibit a significantly higher pH, an increased luminal area and a higher organ to body weight ratio, suggesting an aletered epididymal microenvironment

enlarged epididymis ( J:112876 )

♂ • male homozygotes display an increased luminal area of epididymal ducts relative to wild-type males

increased epididymis weight ( J:112876 )

♂ • male homozygotes display an increased epididymis/body weight ratio relative to wild-type males

male infertility ( J:112876 )

♂ • when mated to wild-type females, male homozygotes are unable to give rise to pregnancies and produce offspring

♂ • however, male homozygotes are able to mate, ejaculate and produce macroscopically normal vaginal plugs

abnormal sperm physiology ( J:112876 )

♂ • male homozygotes show a significantly higher epididymal luminal fluid pH relative to wild-type males (pH = 6.9 vs pH = 6.4, respectively)

♂ • post-testicular sperm maturation is impaired, due to failure of proper acidification of epididymal luminal content caused by defective narrow and clear cell function

impaired sperm migration in female genital tract ( J:112876 )

♂ • despite normal motility, an insufficient number of mutant sperm reach the female genital tract, as shown by direct sperm counts from flushed uteri

cellular

kinked sperm flagellum ( J:112876 )

♂ • male homozygotes show a significantly higher number of sperm with tail angulations than wild-type males

impaired sperm migration in female genital tract ( J:112876 )

♂ • despite normal motility, an insufficient number of mutant sperm reach the female genital tract, as shown by direct sperm counts from flushed uteri

Genotype
MGI:2679654

hm2

• Allelic Composition: Foxi1^tm1Sven/Foxi1^tm1Sven
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

perinatal lethality, incomplete penetrance ( J:51291 )

• approximately 50% of homozygous animals die perinatally

behavior/neurological

absent pinna reflex ( J:51291 )

• homozygotes have no Preyer's reflex

impaired swimming ( J:51291 )

• 81% of homozygotes are poor swimmers: they sink under the surface or swim with their body tilted to one side

head tilt ( J:51291 )

• at 3 weeks, homozygotes display head tilting

hyperactivity ( J:51291 )

• at 3 weeks, homozygotes exhibit hyperactivity and a pathological reaching response

circling ( J:51291 )

• at 3 weeks, homozygotes exhibit behavioral deficits associated with vestibular dysfunction, such as waltzer/shaker-like circling behavior

hearing/vestibular/ear

abnormal inner ear morphology ( J:51291 )

• in homozygotes, the bony compartment in which the inner ear resides is severely malformed

• the inner ear is replaced by a large, irregular and continuous cavity, similar to a group of human congenital inner ear malformations called 'common cavity'

absent cochlea ( J:51291 )

absent inner ear vestibule ( J:51291 )

• the entire vestibulum is absent

impaired hearing ( J:51291 )

• in homozygotes, absence of a Preyer's reflex indicates a profound hearing impairment

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:51291 )

N • homozygotes have normal serum levels of sodium, potassium and creatinine relative to wild-type

renal/urinary system

renal/urinary system phenotype ( J:51291 )

N • homozygotes display no signs of structural malformations in the kidney at the macro- and microscopic level

nervous system

nervous system phenotype ( J:51291 )

N • homozygotes display no signs of structural aberrations in brain

Genotype
MGI:3056282

hm3

• Allelic Composition: Foxi1^tm1Sven/Foxi1^tm1Sven
• Genetic Background: involves: CD-1

hearing/vestibular/ear

abnormal inner ear morphology ( J:82307 )

inner ear cyst ( J:82307 )

• homozygotes display cystic dilatation of the inner ears at E18.5

abnormal cochlea morphology ( J:82307 )

• at E16.5, the basal turn of the cochlea is larger while the apical turn has formed an apical cyst

absent cochlear modiolus ( J:82307 )

abnormal common crus morphology ( J:82307 )

• at E16.5, homozygotes show a prominent expansion of the common crus

dilated lateral semicircular canal ( J:82307 )

• at E16.5, homozygotes show a prominent expansion of the lateral semicircular canal

dilated posterior semicircular canal ( J:82307 )

• at E16.5, homozygotes show a prominent expansion of the posterior semicircular canal, common crus and ampullae

abnormal membranous labyrinth morphology ( J:82307 )

• at E16.5, the entire membranous labyrinth appears enlarged; no major aberrations are observed up to E13.5

enlarged utricle ( J:82307 )

• at E16.5, the mutant utricle is significantly enlarged relative to wild-type

enlarged vestibular saccule ( J:82307 )

• at E16.5, the mutant saccule is significantly enlarged relative to wild-type

dilated endolymphatic duct ( J:82307 )

• at E16.5, homozygotes exhibit a pronounced expansion of the endolymphatic compartment

• by P12, the peri- and endolymphatic compartments of the inner ear have been replaced by a common irregular cavity

dilated endolymphatic sac ( J:82307 )

• at E16.5, homozygotes exhibit a severe dilatation of the endolymphatic sac

absent otoliths ( J:82307 )

• homozygotes show complete absence of the normally white utricular and saccular otoconia found in wild-type, suggesting defective crystallization of calcium carbonate crystals

absent endocochlear potential ( J:82307 )

• homozygotes lack an endocochlear potential indicating a primary defect in fluid homeostasis in the inner ear

deafness ( J:82307 )

• homozygotes are deaf

craniofacial

abnormal temporal bone morphology ( J:82307 )

• the mutant temporal bone is thinner adjacent to the inner ear relative to wild-type

• at E18.5, homozygotes show abnormal integration of the otic capsule into the temporal bone anlagen associated with ectopic cartilage and/or bone formation

cellular

increased apoptosis ( J:82307 )

• at E16.5, homozygotes show a minor increase of apoptosis in a small mesenchymal cell population adjacent to the expanded endolymphatic duct

nervous system

abnormal cerebellum morphology ( J:82307 )

• the mutant cerebellum appears compressed due to the severe expansion of the inner ear

renal/urinary system

renal tubular acidosis ( J:90907 )

• homozygotes fail to secrete protons in response to both a chronic as well as an acute acidic load

• homozygotes are unable to acidify the urine and display a reduced systemic buffer capacity

• homozygotes develop renal tubular acidosis in response to a prolonged acidic load

increased urine pH ( J:90907 )

• homozygotes produce urine with elevated pH relative to wild-type

abnormal kidney collecting duct epithelium morphology ( J:90907 )

• homozygotes show ultrastructural changes in the epithelium of the cortical collecting duct (CCD)

• mitochondria-rich cells with a protruding "tussock-like" apex are missing from mutants CCDs

• the distal nephron epithelium with its two major cell types (principal and intercalated cells) is replaced by a single cell type positive for both principal and intercalated cell markers

homeostasis/metabolism

renal tubular acidosis ( J:90907 )

• homozygotes fail to secrete protons in response to both a chronic as well as an acute acidic load

• homozygotes are unable to acidify the urine and display a reduced systemic buffer capacity

• homozygotes develop renal tubular acidosis in response to a prolonged acidic load

increased urine pH ( J:90907 )

• homozygotes produce urine with elevated pH relative to wild-type

skeleton

abnormal temporal bone morphology ( J:82307 )

• the mutant temporal bone is thinner adjacent to the inner ear relative to wild-type

• at E18.5, homozygotes show abnormal integration of the otic capsule into the temporal bone anlagen associated with ectopic cartilage and/or bone formation

growth/size/body

inner ear cyst ( J:82307 )

• homozygotes display cystic dilatation of the inner ears at E18.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Pendred Syndrome		DOID:0060744	OMIM:274600	J:83207

Genotype
MGI:2679655

ht4

• Allelic Composition: Foxi1^tm1Sven/Foxi1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

perinatal lethality, incomplete penetrance ( J:51291 )

• approximately one fourth of heterozygous animals die at birth; animals are otherwise healthy and fertile

behavior/neurological

behavior/neurological phenotype ( J:51291 )

N • in contrast to homozygotes, heterozygotes display a normal reaching response and a normal swimming ability

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:51291 )

N • in contrast to homozygotes, heterozygotes display a normal Preyer's reflex and normal inner ear structure