Analysis Tools
reproductive system
 |
• female mice exhibit delayed puberty
|
|
|
• vaginal opening is significantly delayed and occurs an average of 5 days later than in wild-type females (P32 versus P27)
• however, vaginal opening occurs at a body size of ~15 gm, similar to wild-type females
|
|
|
• female mice never achieve cyclicity and exhibit highly erratic estrus cycles, with no apparent pattern of timing or duration of cycle stages
|
|
|
• female mice achieve first estrus on P43, that is, 10 days later than wild-type females (P33)
• females have first estrus at a body size of ~15 gm, whereas wild-type females have first estrus at ~18 gm
|
taste/olfaction
|
• 10% decrease in the number of basal cells
|
|
• cilia markers are consistently patchy indicating regional decreases in cilia components
• patchy distribution is confirmed by SEM
|
|
• the normal arrangement in parallel stacked columns in the epithelium is lost
|
|
• 30% reduction in number
|
|
• E10.5 embryos show a 49% reduction in phospho-histone H3-positive proliferating cells in the olfactory placode relative to wild-type controls
• embryos exhibit a significant reduction in TUNEL-positive cells in the nasal region relative to wild-type embryos at E10.5 (-21%), E11.5 (-11%) and E12.5 (-13%]
• expression levels of Otx2, Bmp4 and Fgfr1 (involved in proliferation and/or neurogenesis) are significantly decreased in the olfactory placode at E10.5
• however, the size of the E10.5 olfactory placode is normal and invagination of the olfactory placode to form the olfactory pit appears unaffected
|
|
• 50% reduction in proliferating basal cells in adults
|
|
• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed
|
|
• little to no response to 6 different odorants (amyl acetate, octanal, haptaldehyde, hexanal, eugenol, and carvone) tested by electro-olfactogram
|
nervous system
|
• GnRH neurogenesis is impaired resulting in reduced GnRH neurons in embryos and adult mice
|
|
• the normal arrangement in parallel stacked columns in the epithelium is lost
|
|
• 30% reduction in number
|
|
• both adult male and female mice show a 35% reduction in the total number of GnRH-positive neuron cell bodies in the hypothalamus relative to wild-type controls
• embryos show a 30% reduction in the total number of GnRH-positive neurons in the nasal region at E11.5 and E12.5, consistent with fewer GnRH neurons in the adult hypothalamus
• however, GnRH neurons show normal distribution throughout the rostral-caudal axis from the nasal region to the cerebellum, suggesting normal GnRH neuronal migration
|
|
• adult male and female mice show, respectively, a 51% and 54% reduction in anti-GnRH immunofluorescence in the median eminence
• however, immunofluorescence of arginine vasopressin (AVP)-positive fibers in the median eminence is normal
|
|
• expression levels of Gnrhr (gonadotropin releasing hormone receptor) are significantly reduced in the adult pituitary gland
|
|
• decreased length
|
|
• decreased length
|
|
• decreased length but not width
• however, intact OMP-positive olfactory bulb glomeruli are present
|
|
• expression levels of Gnrh1 (gonadotropin releasing hormone 1) and Otx2 (orthodenticle homeobox 2) are significantly reduced in the adult hypothalamus
|
|
• reduced olfactory interneuron activity
|
|
• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed
|
homeostasis/metabolism
| N |
• both male and female mice show normal serum levels of growth hormone (GH) and insulin-like growth factor I (IGF1) relative to wild-type controls
• 2 h after administration of leuprolide, a GnRH agonist, both male and female mice show a normal increase in serum levels of LH and FSH relative to similarly treated wild-type controls
• female mice show normal serum levels of insulin and leptin relative to wild-type females
• 2 h after administration of antide, a gonadotropin-releasing hormone (GnRH) antagonist, male mice show a normal decrease in serum levels of LH and FSH relative to similarly treated wild-type controls
|
|
|
• at late estrus, 3-4-month-old female mice show an 83% reduction in serum FSH levels relative to wild-type controls
• in contrast, male mice show normal serum FSH levels
|
|
• at late estrus, 3-4-month-old female mice show a 74% reduction in serum LH levels relative to wild-type controls
• male mice show an 86% reduction in serum LH levels relative to wild-type controls
|
cellular
|
• cilia markers are consistently patchy indicating regional decreases in cilia components
• patchy distribution is confirmed by SEM
|
|
• embryos exhibit a significant reduction in TUNEL-positive cells in the nasal region relative to wild-type embryos at E10.5 (-21%), E11.5 (-11%) and E12.5 (-13%]
|
|
• GnRH neurogenesis is impaired resulting in reduced GnRH neurons in embryos and adult mice
|
|
• E10.5 embryos show a 49% reduction in phospho-histone H3-positive proliferating cells in the olfactory placode relative to wild-type controls
|
endocrine/exocrine glands
| N |
• mice show normal pituitary gland histology at E10.5, E14.5, E18.5 and in adulthood
|
|
• both adult male and female mice show a 35% reduction in the total number of GnRH-positive neuron cell bodies in the hypothalamus relative to wild-type controls
• embryos show a 30% reduction in the total number of GnRH-positive neurons in the nasal region at E11.5 and E12.5, consistent with fewer GnRH neurons in the adult hypothalamus
• however, GnRH neurons show normal distribution throughout the rostral-caudal axis from the nasal region to the cerebellum, suggesting normal GnRH neuronal migration
|
|
• adult male and female mice show, respectively, a 51% and 54% reduction in anti-GnRH immunofluorescence in the median eminence
• however, immunofluorescence of arginine vasopressin (AVP)-positive fibers in the median eminence is normal
|
|
• expression levels of Gnrhr (gonadotropin releasing hormone receptor) are significantly reduced in the adult pituitary gland
|
growth/size/body
|
• 10% decrease in the number of basal cells
|
|
• cilia markers are consistently patchy indicating regional decreases in cilia components
• patchy distribution is confirmed by SEM
|
|
• the normal arrangement in parallel stacked columns in the epithelium is lost
|
|
• 30% reduction in number
|
|
• both male and female mice are significantly smaller than wild-type controls
|
respiratory system
|
• 10% decrease in the number of basal cells
|
|
• cilia markers are consistently patchy indicating regional decreases in cilia components
• patchy distribution is confirmed by SEM
|
|
• the normal arrangement in parallel stacked columns in the epithelium is lost
|
|
• 30% reduction in number
|
|
• 50% reduction in proliferating basal cells in adults
|
|
• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed
|
craniofacial
|
• 10% decrease in the number of basal cells
|
|
• cilia markers are consistently patchy indicating regional decreases in cilia components
• patchy distribution is confirmed by SEM
|
|
• the normal arrangement in parallel stacked columns in the epithelium is lost
|
|
• 30% reduction in number
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:148116 , J:174086 | |
