Phenotypes Associated with This Genotype

Genotype
MGI:2175062

• Allelic Composition: Hesx1^tm1Icar/Hesx1^tm1Icar
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:47920 )

• most severely affected pups only die shortly after birth

postnatal lethality, incomplete penetrance ( J:47920 )

• 75% of mice dead by 3 weeks

nervous system

small vomeronasal organ ( J:47920 )

• the vomeronasal organs are reduced

decreased embryonic neuroepithelium thickness ( J:47920 )

• at E11.5 and E12.5, in mildly affected mice the neuroepithelium is thin compared to in wild-type and heterozygous mice

absent Rathke's pouch ( J:47920 )

• at E12.5, in severely affected mice Rathke's pouch is absent

bifurcated Rathke's pouch ( J:47920 )

• all mice display defects in Rathke's pouch such that it is abnormally bifurcated

small adenohypophysis ( J:47920 )

• the anterior lobe of the pituitary is smaller than in wild-type mice and less intimately associated with the posterior lobe

absent pituitary infundibular stalk ( J:47920 )

• at E12.5, severely affected mice display no sign of infundibulum development

abnormal forebrain development ( J:47920 )

• at E8.5, prospective forebrain tissue is reduced

• forebrain defects are variable between hemispheres and mice

• at E12.5, severely affected mice display reduced forebrain size with no sign of telencephalic vesicles

• nerve fibers are present but fail to cross the midline

• defects are more pronouced on one side of the mice than the other

abnormal telencephalon development ( J:47920 )

• many mice display a disruption of left-right asymmetry of the telecephalic vessicle, eye, and olfactory placode

small embryonic telencephalon ( J:47920 , J:142649 )

• severely affected mice (5%) lack or exhbit a reduction in telencephalic vesicles, olfactory placodes and frontonasal mass (J:47920)

• at E11.5 and E12.5, mildly affected mice display reduced telencephalic vesicles (J:47920)

• however, mildly affected mice exhibit normal medial and lateral ganglionic eminences (J:47920)

• telencephalic vesicles are reduced in size at 12.5 dpc (J:142649)

abnormal midbrain-hindbrain boundary development ( J:135132 )

• at 9.5 dpc (days post coitum), elevated apoptosis is observed relative to wild-type at level of midbrain-hindbrain boundary

decreased forebrain size ( J:47920 , J:135132 )

• forebrain reduction is variable depending on the severity of phenotype (J:47920)

• at E12.5, severely affected mice display reduced forebrain size with no sign of telencephalic vesicles (J:47920)

• reduction of anterior forebrain (AFB) tissue is detected at 8- to 10-somite (8.5 dpc) stage, based upon expression of markers Six3, Pax2, Pax6 and Fgf8 (J:135132)

• at presomitic stages, expression domains of these markers are identical to controls (J:135132)

absent hippocampal commissure ( J:47920 )

• the dorsal and ventral hippocampal commissures are absent in 2 of 3 mice that also lacked the anterior commissure and the corpus callosum

absent anterior commissure ( J:47920 )

• absent in 3 of 4 mice

abnormal hypothalamus morphology ( J:47920 )

• all mice display ventral midline defects in the hypothalamus with the floor of the hypothalamus is expanded

abnormal telencephalon morphology ( J:47920 , J:135132 )

• telencephalic midline structures are abnormal (J:47920)

• cell death in roof plate of telencephalon is reduced compared to normal littermates at 9.5 dpc (J:135132)

absent corpus callosum ( J:47920 )

• in 3 of 4 mice

olfactory bulb hypoplasia ( J:47920 )

• the olfactory bulbs are hypoplastic and lack glomerular and mitral cell layers

abnormal septum pellucidum morphology ( J:47920 )

• in 25% of mice the septum pellucidum is missing

respiratory system

abnormal nasal pit morphology ( J:47920 )

• mice display hypoplastic and frequently asymmetric olfactory pits

abnormal nasal placode morphology ( J:47920 )

• severely affected mice (5%) lack or exhbit a reductin in telencephalic vesicles, olfactory placodes and frontonasal mass

• many mice display a disruption of left-right asymmetry of the telecephalic vessicle, eye, and olfactory placode

• at E12.5, in severely affected mice the olfactory placodes are absent

abnormal nasal cavity morphology ( J:47920 )

• the nasal cavitis are hypoplastic and the olfactory epithelium at the rostral extreme of the cavities is aplastic

small vomeronasal organ ( J:47920 )

• the vomeronasal organs are reduced

abnormal olfactory epithelium morphology ( J:47920 )

• the olfactory epithelium at the rostral extreme of the nasal cavities is aplastic

• however, caudal epithelium is normal

vision/eye

abnormal eye morphology ( J:47920 )

• at birth, severely affected mice display absent or micropthalamic eyes

• mildly affected mice display abnormal eye morphology in only one eye

abnormal optic cup morphology ( J:47920 )

• at E12.5, in severely affected mice the optic cup and ectodermal derivatives such as the optic lenses, olfactory placodes and Rathke's pouch are absent

abnormal optic vesicle formation ( J:47920 )

• the optic vesicles are hypoplastic and frequently assymetric

enophthalmos ( J:47920 )

• when eyes are present, they are located more posteriorly than in wild-type mice and remain buried in the orbit

microphthalmia ( J:47920 )

• at birth, severely affected mice display absent or micropthalamic eyes

anophthalmia ( J:47920 , J:142649 )

• at birth, severely affected mice display absent or micropthalamic eyes (J:47920)

• embryos lack eyes at 12.5 days post coitum (dpc) (J:142649)

craniofacial

abnormal craniofacial morphology ( J:47920 )

• mildly affected mice display craniofacial dysplasia

abnormal frontonasal prominence morphology ( J:142649 )

• frontonasal mass development is impaired by 12.5 dpc

abnormal nasal pit morphology ( J:47920 )

• mice display hypoplastic and frequently asymmetric olfactory pits

abnormal nasal placode morphology ( J:47920 )

• severely affected mice (5%) lack or exhbit a reductin in telencephalic vesicles, olfactory placodes and frontonasal mass

• many mice display a disruption of left-right asymmetry of the telecephalic vessicle, eye, and olfactory placode

• at E12.5, in severely affected mice the olfactory placodes are absent

abnormal nasal cavity morphology ( J:47920 )

• the nasal cavitis are hypoplastic and the olfactory epithelium at the rostral extreme of the cavities is aplastic

small vomeronasal organ ( J:47920 )

• the vomeronasal organs are reduced

abnormal olfactory epithelium morphology ( J:47920 )

• the olfactory epithelium at the rostral extreme of the nasal cavities is aplastic

• however, caudal epithelium is normal

short snout ( J:47920 )

• at birth, severely affected mice display small head size, short nose and absent or micropthalamic eyes

hearing/vestibular/ear

absent otic vesicle ( J:47920 )

• at E8.5, mice lack otic vesicles

taste/olfaction

abnormal nasal placode morphology ( J:47920 )

• severely affected mice (5%) lack or exhbit a reductin in telencephalic vesicles, olfactory placodes and frontonasal mass

• many mice display a disruption of left-right asymmetry of the telecephalic vessicle, eye, and olfactory placode

• at E12.5, in severely affected mice the olfactory placodes are absent

abnormal olfactory epithelium morphology ( J:47920 )

• the olfactory epithelium at the rostral extreme of the nasal cavities is aplastic

• however, caudal epithelium is normal

endocrine/exocrine glands

absent Rathke's pouch ( J:47920 )

• at E12.5, in severely affected mice Rathke's pouch is absent

bifurcated Rathke's pouch ( J:47920 )

• all mice display defects in Rathke's pouch such that it is abnormally bifurcated

small adenohypophysis ( J:47920 )

• the anterior lobe of the pituitary is smaller than in wild-type mice and less intimately associated with the posterior lobe

absent pituitary infundibular stalk ( J:47920 )

• at E12.5, severely affected mice display no sign of infundibulum development

embryo

decreased embryonic neuroepithelium thickness ( J:47920 )

• at E11.5 and E12.5, in mildly affected mice the neuroepithelium is thin compared to in wild-type and heterozygous mice

growth/size/body

abnormal nasal cavity morphology ( J:47920 )

• the nasal cavitis are hypoplastic and the olfactory epithelium at the rostral extreme of the cavities is aplastic

small vomeronasal organ ( J:47920 )

• the vomeronasal organs are reduced

abnormal olfactory epithelium morphology ( J:47920 )

• the olfactory epithelium at the rostral extreme of the nasal cavities is aplastic

• however, caudal epithelium is normal

short snout ( J:47920 )

• at birth, severely affected mice display small head size, short nose and absent or micropthalamic eyes

microcephaly ( J:47920 )

• at birth, severely affected mice display small head size, short nose and absent or micropthalamic eyes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypopituitarism		DOID:9406		J:47920
septooptic dysplasia		DOID:0060857	OMIM:182230	J:47920 , J:60068