Analysis Tools
mortality/aging
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• only rare homozygotes survive through adulthood
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• homozygotes are significantly underrepresented from E13 onwards with less than 6% detected at E14.5 and beyond E17.5
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• most homozygotes are either stillborn or die within 1-2 days after birth
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growth/size/body
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• at E12.5, embryos show abnormal facial features often associated with midline defects
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• at E18.5, embryos show a narrow mid-facial region
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• at E12.5
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• at 12 weeks of age, homozygotes show a severely reduced and curved nasal midline
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the olfactory bulb, indicating a severe deprivation of ciliary axoneme structures
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• at E18.5
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• homozygotes show significant developmental defects and growth retardation at E13.5
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ovary cyst
(
J:257035
)
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• 33% of female pups exhibit ovarian (hemorrhagic) cysts
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• at 1 week and 25 weeks of age, homozygotes show a significantly higher BMI than wild-type controls
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microcephaly
(
J:257035
)
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• the head is notably smaller at E18.5
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• neonates show significant developmental defects and growth retardation at P1
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skeleton
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• 32% of homozygotes show skeletal defects; skeletons are hypoplastic with reduced or absent bone mineralization
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• at 12 weeks of age, homozygotes show a small lower jaw
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• abnormal hearts are sometimes accompanied by thoracic skeletal defects
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• skeletons exhibit reduced or absent bone mineralization
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limbs/digits/tail
syndactyly
(
J:257035
)
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• forelimbs exhibit abnormal digit separation at E13.5 and digit fusion at P1
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short limbs
(
J:257035
)
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• at P1
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craniofacial
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• at E18.5, embryos show multiple defects in midline craniofacial structures
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• at 12 weeks of age, homozygotes show a small lower jaw
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• at E12.5, homozygotes show fusion of the medial nasal processes
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• at E18.5, embryos show hypoplasia of the olfactory pit
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• at E12.5, embryos show abnormal facial features often associated with midline defects
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• at E18.5, embryos show a narrow mid-facial region
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• at E12.5
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• at 12 weeks of age, homozygotes show a severely reduced and curved nasal midline
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the olfactory bulb, indicating a severe deprivation of ciliary axoneme structures
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• at E18.5
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vision/eye
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• 15% of homozygotes show eye defects, including single/absent eyes indicating failed eye field development
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• at E18.5, embryos show hypoplasia of the optic eminence
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• some homozygotes display closely spaced eyes
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anophthalmia
(
J:257035
)
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• in some cases
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nervous system
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• at E12.5, the relative proportion of GnRH-positive neurons is 9.5% higher under the cribriform plate area but 5.9% lower in the forebrain area compared to wild-type controls, suggesting delayed embryonic migration of GnRH neurons
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• at E18.5, embryos show hypoplasia of the neuroepithelium
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• the total number of gonadotrophin-releasing hormone (GnRH)-positive neurons is significantly reduced in whole embryo heads at E12.5
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• homozygotes exhibit several features of holoprosencephaly (HPE) associated with Hh signal deficiency
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hydrocephaly
(
J:257035
)
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• 33% of pups exhibit hydrocephalus
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• at E18.5
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• at 8 weeks of age, the choroid plexus shows morphological changes and lack of ciliary acetylated tubulin (ACT) staining, indicating fewer epithelial cilia relative to wild-type controls
• however, the overall ciliary axonemal structure is normal
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• at E18.5, embryos show a partially divided forebrain
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• embryos display a bifurcation of the anterior pituitary lobe
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the median eminence, indicating a severe deprivation of ciliary axoneme structures
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• embryos display dysmorphogenesis of the pituitary gland
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• embryos display abnormal shaping of the lumen of Rathkes pouch
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• at E18.5
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• at 12 weeks of age, homozygotes show olfactory bulb (OB) dysgenesis
• at E18.5, the OB appears rudimentary and fails to separate
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• at E18.5, homozygotes show olfactory bulb hypoplasia with incomplete separation of the telencephalon similar to that in lobar holoprosencephaly
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exencephaly
(
J:257035
)
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• in some cases, homozygotes exhibit exencephaly with no signs of spina bifida
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• homozygotes exhibit hypothalamic GnRH deficiency
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cardiovascular system
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• 31% of embryos show heart defects
• abnormal hearts are sometimes accompanied by thoracic skeletal defects and lung airway abnormalities
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• a double outlet right ventricle is observed at E12.5
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• ventricular septal defects are observed at E12.5
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reproductive system
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• male homozygotes show a high frequency (>50%) of morphologically abnormal sperm leading to subfertility or infertility
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• male homozygotes show a reduced anogenital distance index
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• ovaries show absence of antral follicles
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• widespread atresia is observed
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• ovaries show arrested follicle development
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small ovary
(
J:257035
)
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ovary cyst
(
J:257035
)
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• 33% of female pups exhibit ovarian (hemorrhagic) cysts
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• at 6 weeks of age, male homozygotes show vacuolated seminiferous tubules containing fewer spermatozoa and spermatids
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• at 6 weeks of age
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small testis
(
J:257035
)
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small penis
(
J:257035
)
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• male homozygotes exhibit microphallus
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• uteri exhibit thin and poorly differentiated walls
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small uterus
(
J:257035
)
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• male homozygotes show underdeveloped external genitalia
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• homozygotes exhibit delayed puberty
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• the timing of balanopreputial separation is significantly delayed relative to heterozygous and wild-type controls
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• female homozygotes exhibit dysregulated estrous cycles
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• male homozygotes exhibit severely reduced fertility or infertility
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• male homozygotes exhibit severely reduced fertility or infertility
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cellular
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• mouse embryo fibroblasts (MEFs) derived from E12.5 embryos show defective ciliogenesis with a significant reduction in the length of the ciliary axoneme and the frequency of ciliated cells, but no defects in the formation of the basal body
• brain shows virtually absent ciliary acetylated tubulin (ACT) staining in the olfactory bulb and median eminence
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the olfactory bulb, indicating a severe deprivation of ciliary axoneme structures
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• male homozygotes show a high frequency (>50%) of morphologically abnormal sperm leading to subfertility or infertility
|
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• at E12.5, the relative proportion of GnRH-positive neurons is 9.5% higher under the cribriform plate area but 5.9% lower in the forebrain area compared to wild-type controls, suggesting delayed embryonic migration of GnRH neurons
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respiratory system
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• at E18.5, embryos show hypoplasia of the olfactory pit
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• at 12 weeks of age, homozygotes show a severely reduced and curved nasal midline
|
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the olfactory bulb, indicating a severe deprivation of ciliary axoneme structures
|
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• at E18.5
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• abnormal hearts are sometimes accompanied by lung airway abnormalities
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endocrine/exocrine glands
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• the total number of gonadotrophin-releasing hormone (GnRH)-positive neurons is significantly reduced in whole embryo heads at E12.5
|
|
• embryos display a bifurcation of the anterior pituitary lobe
|
|
• ciliary acetylated tubulin (ACT) staining is virtually absent in the median eminence, indicating a severe deprivation of ciliary axoneme structures
|
|
• embryos display dysmorphogenesis of the pituitary gland
|
|
• embryos display abnormal shaping of the lumen of Rathkes pouch
|
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• at E18.5
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• ovaries show absence of antral follicles
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• widespread atresia is observed
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• ovaries show arrested follicle development
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small ovary
(
J:257035
)
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ovary cyst
(
J:257035
)
|
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• 33% of female pups exhibit ovarian (hemorrhagic) cysts
|
|
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• at 6 weeks of age, male homozygotes show vacuolated seminiferous tubules containing fewer spermatozoa and spermatids
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• at 6 weeks of age
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small testis
(
J:257035
)
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digestive/alimentary system
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• at E12.5
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• male homozygotes show a reduced anogenital distance index
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renal/urinary system
small penis
(
J:257035
)
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• male homozygotes exhibit microphallus
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taste/olfaction
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• ciliary acetylated tubulin (ACT) staining is virtually absent in the olfactory bulb, indicating a severe deprivation of ciliary axoneme structures
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embryo
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• homozygotes show significant developmental defects and growth retardation at E13.5
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• at E18.5, embryos show hypoplasia of the neuroepithelium
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ciliopathy | DOID:0060340 | J:257035 | ||
| Kallmann syndrome | DOID:3614 | J:257035 | ||
