Mouse Genome Informatics
hm
    Eya1tm1Rilm/Eya1tm1Rilm
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• all homozygotes die at birth

craniofacial
• at E12.5, the cartilage primordium of the temporal bone is severely affected
• hyoid bone is malformed
• lesser horns are malformed
• the incus is present but malformed
• the short process of the malleus is usually absent
• the stapes is usually absent
• middle ear ossicles are frequently fused
• on a C57BL/6 background abnormal fusion of the palatal shelves to the nasal septum is seen
• on mixed 129 or 129 and BALB/c backgrounds cleft secondary palate is seen
• preauricular pits are seen
• atresia of the external auditory canal is seen
• the external auditory meati are absent or when present end blindly
• the auricles are missing or malformed

endocrine/exocrine glands
• unilateral or bilateral persistence of ultimobranchial bodies outside the thyroid gland is seen at E15.5
• organ primordia for the thymus are not seen at E12.0 (J:79848)
• hypoplastic thyroid lobes with fewer calcitonin producing cells are seen
• some mutants lack an isthmus in the thyroid gland

hearing/vestibular/ear
• increased cell death in the otic epithelium is first noted at ~E9.0, with numerous apoptotic bodies found in the rims of the otic cup, as shown by TUNEL analysis (J:119574)
• at E9.5, increased cell death is apparent in the lateral wall of the otic vesicle, while a few apoptotic cells are also observed in the medial wall of the otic vesicle (J:119574)
• by E10.5, apoptotic cells are found throughout the otic vesicle (J:119574)
• at E8.5, the number of BrdU-labeled cells in the mutant otic placode is ~80% of wild-type embryos
• at E9.0 and E9.5, BrdU-positive cells are significantly reduced in the otic cup and vesicle, and are only 60% and 40% of wild-type embryos, respectively, in the otic placode
• preauricular pits are seen
• atresia of the external auditory canal is seen
• the external auditory meati are absent or when present end blindly
• the auricles are missing or malformed
• the otic vesicle from which inner ear structures arise fails to form, associated with increased apoptosis (J:57313)
• at E11.5, homozygotes show a significant size reduction of the otocyst relative to wild-type mice
• marker gene analyses at different stages indicate that primordia fated to form the endolymphatic duct are present but fail to outgrow normally
• at E12.5, homozygotes display two vesicle-like structures, with the one located medially showing strong Foxi1 expression in all 6 embryos examined, indicating that it is the endolymphatic duct/sac
• at E10.5 to E11.5, all homozygotes lack visible development of the cochlea
• at E10.5 to E11.5, all homozygotes lack visible development of the vestibule
• at E10.5 to E11.5, an abnormal vesicular structure is formed posteroventrally in 10 ears of 7 mutant embryos instead of a normal endolymphatic duct
• marker gene analysis indicates that development of endolymphatic duct is initiated but fails to form a normal structure
• the endolymphatic duct is absent or malformed (J:57313)
• at E10.5 to E11.5, a normal outgrowth of the endolymphatic duct is absent in all 20 ears of 10 mutant embryos studied; narrower dorsal tips are observed (J:119574)
• paintfilling confirms absence of the outgrowth of endolymphatic duct in all 8 mutant ears analyzed (J:119574)
• the tympanic cavity does not form
• tympanic bulla is absent
• the incus is present but malformed
• the short process of the malleus is usually absent
• the stapes is usually absent
• middle ear ossicles are frequently fused
• the eardrums are malformed

immune system
• organ primordia for the thymus are not seen at E12.0 (J:79848)

renal/urinary system
• the metanephric mesenchyme undergoes apoptosis, disappearing by E12.5
• bilateral kidney agenesis is seen in all homozygotes
• ureters are absent in all homozygotes due to failure of ureteric bud outgrowth and metanephric induction
• the ureteric bud fails to form

skeleton
• at E12.5, the cartilage primordium of the temporal bone is severely affected
• hyoid bone is malformed
• lesser horns are malformed
• the incus is present but malformed
• the short process of the malleus is usually absent
• the stapes is usually absent
• middle ear ossicles are frequently fused
• lateral processes of the thyroid cartilage, which normally connect with the cricoid cartilage, are absent or malformed
• T7 ribs do not fuse with the sternum
• the ischium and pubis are fused
• the ischium and pubis are fused
• ribs are fused bilaterally
• the mutant atlas and axis are fused

vision/eye

nervous system
• the geniculate ganglion is absent

embryogenesis
• a persistent cleft of the first pharyngeal pouch is seen at E10.5 (J:57313)
• increased apoptosis is seen in the surface ectoderm of the 3rd and 4th pouches (J:79848)
• unilateral or bilateral persistence of ultimobranchial bodies outside the thyroid gland is seen at E15.5

hematopoietic system
• organ primordia for the thymus are not seen at E12.0 (J:79848)

digestive/alimentary system
• on a C57BL/6 background abnormal fusion of the palatal shelves to the nasal septum is seen
• on mixed 129 or 129 and BALB/c backgrounds cleft secondary palate is seen

respiratory system
• lateral processes of the thyroid cartilage, which normally connect with the cricoid cartilage, are absent or malformed

cellular
• the metanephric mesenchyme undergoes apoptosis, disappearing by E12.5
• increased cell death in the otic epithelium is first noted at ~E9.0, with numerous apoptotic bodies found in the rims of the otic cup, as shown by TUNEL analysis (J:119574)
• at E9.5, increased cell death is apparent in the lateral wall of the otic vesicle, while a few apoptotic cells are also observed in the medial wall of the otic vesicle (J:119574)
• by E10.5, apoptotic cells are found throughout the otic vesicle (J:119574)
• at E8.5, the number of BrdU-labeled cells in the mutant otic placode is ~80% of wild-type embryos
• at E9.0 and E9.5, BrdU-positive cells are significantly reduced in the otic cup and vesicle, and are only 60% and 40% of wild-type embryos, respectively, in the otic placode

growth/size
• on a C57BL/6 background abnormal fusion of the palatal shelves to the nasal septum is seen
• on mixed 129 or 129 and BALB/c backgrounds cleft secondary palate is seen
• preauricular pits are seen
• atresia of the external auditory canal is seen
• the external auditory meati are absent or when present end blindly
• the auricles are missing or malformed

Mouse Models of Human Disease
OMIM IDRef(s)
Branchiootorenal Syndrome 1; BOR1 113650 J:57313