Analysis Tools
mortality/aging
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• 3 of 14 homozygotes surviving postnatally die at 8 weeks due to complications from hydrocephalus; the remainig homozygotes survive through 10 months of age
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• most homozygotes die perinatally
• only 5% of homozygotes survive to adulthood (at least 10 months), in the absence of developmental defects in kidney, lung, heart, liver or brain (at the level of hippocampus, thalamus/basal ganglia, and cerebellum)
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behavior/neurological
hyperactivity
(
J:60409
)
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• at 10 weeks, surviving homozygotes are strikingly hyperactive, travelling longer distances and spending more time moving than sex-matched wild-type or heterozygous mice in the open-field test
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• the distance traveled over an one-hour period is on average 10x greater than that covered by wild-type or heterozygous mice
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craniofacial
cranioschisis
(
J:60409
)
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• homozygotes commonly exhibit cranioschisis
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• at E15.5, homozygotes display prominent palate defects
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• at E13.5, homozygotes exhibit nasal septal defects
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nervous system
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• at E13.5, homozygotes exhibit ectopic regions of neurogenesis, with supernumerary developing neurons abnormally distributed in the subventricular zone
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• mature neurons developing in ectopic regions fail to migrate to their proper position in the cortex
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• homozygotes exhibit abnormal thickening of the neuroepithelium as early as E9.5
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• at E9.5, homozygotes frequently fail to close the neural tube
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hydrocephaly
(
J:60409
)
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• at E12.5, the ventricles in the developing mutant brain are compressed, as a result of supernumerary cells in the periventricular zone
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• by E13.5, the increased number of cells in the periventricular zone have invaded and obliterated the lateral ventricles, and the ganglionic eminence is almost undetectable
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• by E13.5, the increased number of cells in the periventricular zone have invaded and obliterated the lateral ventricles, and the ganglionic eminence is almost undetectable
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exencephaly
(
J:60409
)
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• homozygotes commonly exhibit exencephaly
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reproductive system
azoospermia
(
J:60409
)
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• at 2 to 10 months of age, the epidydimis of male homozygotes contains cellular debris and is devoid of viable, mature sperm; however, both Sertoli and Leydig cells are present, and normal secondary sexual features are preserved
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• at 2 to 10 months, surviving male homozygotes exhibit massive degeneration of spermatogonia in the testis
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• adult male homozygotes invariably exhibit patent seminiferous tubules
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• adult female homozygotes are fertile and breed successfully, albeit at a reduced rate
• mutant ovaries show normal follicular development and function and lack atretic follicles
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• adult male homozygotes are infertile
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respiratory system
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• at E13.5, homozygotes exhibit nasal septal defects
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skeleton
cranioschisis
(
J:60409
)
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• homozygotes commonly exhibit cranioschisis
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neoplasm
| N |
• surviving homozygotes do NOT exhibit spontaneous soft tissue tumor formation
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vision/eye
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• at E15.5, homozygotes exhibit retinal thickening
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endocrine/exocrine glands
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• adult male homozygotes invariably exhibit patent seminiferous tubules
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cellular
azoospermia
(
J:60409
)
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• at 2 to 10 months of age, the epidydimis of male homozygotes contains cellular debris and is devoid of viable, mature sperm; however, both Sertoli and Leydig cells are present, and normal secondary sexual features are preserved
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• at 2 to 10 months, surviving male homozygotes exhibit massive degeneration of spermatogonia in the testis
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• cell extracts prepared from mutant MEFs fail to activate procaspase-3 in the presence of dATP
• in response to staurosporine-induced apoptosis, mutant MEFs exhibit the expected morphological features of cell death, but fail to activate caspase-3 or -9
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• at E13.5, homozygotes exhibit ectopic regions of neurogenesis, with supernumerary developing neurons abnormally distributed in the subventricular zone
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• mature neurons developing in ectopic regions fail to migrate to their proper position in the cortex
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hearing/vestibular/ear
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• at E9.5, the neuroepithelium lining the otic vesicles is thickened and poorly organized
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digestive/alimentary system
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• at E15.5, homozygotes display prominent palate defects
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embryo
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• homozygotes exhibit abnormal thickening of the neuroepithelium as early as E9.5
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• at E9.5, homozygotes frequently fail to close the neural tube
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growth/size/body
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• at E15.5, homozygotes display prominent palate defects
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• at E13.5, homozygotes exhibit nasal septal defects
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