Phenotypes Associated with This Genotype

Genotype
MGI:2172824

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:30431 )

• embryonic death continues to occur

perinatal lethality, complete penetrance ( J:30431 )

• some homozygotes are born alive but all are dead within the first day after birth

embryonic lethality during organogenesis, incomplete penetrance ( J:30431 )

• development is normal up to about E12.5

nervous system

abnormal neuron differentiation ( J:30431 )

• premature neurogenesis as indicated by the appearance of neurofilament and L1(+) cells in the telencephalon at E10.5

abnormal neural tube morphology ( J:30431 , J:71074 )

• 70% of embryos have severe neural tube defects (J:30431)

everted embryonic neuroepithelium ( J:30431 )

• everted neuroepithelium

incomplete rostral neuropore closure ( J:30431 )

• fail to fuse at E9.5

kinked neural tube ( J:30431 )

• occasionally seen around E8.5

increased solitary pulmonary neuroendocrine cell number ( J:64088 )

• at E13-E18, significantly more CGRP-positive PNECs (including single and clustered PNECs) are observed than in wild-type or heterozygous mutant lungs

abnormal cochlear hair cell morphology ( J:64679 )

increased cochlear inner hair cell number ( J:64679 , J:70081 )

• nearly complete row of supernumerary inner hair cells (J:70081)

increased cochlear outer hair cell number ( J:64679 , J:70081 )

• some areas with four outer hair cell rows rather than three (J:70081)

increased vestibular hair cell number ( J:64679 , J:70081 )

• significant increase of hair cells on sensory epithelium of utricle and saccule (but to a lesser extent) (J:70081)

abnormal brain development ( J:30431 )

• necrosis starting in some brain regions by E12.5

anencephaly ( J:30431 )

• by E18.5

exencephaly ( J:30431 )

• at E10.5

• everted neuroepithelium

craniofacial

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E12.5 but not at E10.5

vision/eye

abnormal retina neuronal layer morphology ( J:54662 )

• premature neuronal differentiation

disorganized retina layers ( J:54662 )

• disrupted laminar structures in the retina

taste/olfaction

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E12.5 but not at E10.5

hearing/vestibular/ear

abnormal cochlear hair cell morphology ( J:64679 )

increased cochlear inner hair cell number ( J:64679 , J:70081 )

• nearly complete row of supernumerary inner hair cells (J:70081)

increased cochlear outer hair cell number ( J:64679 , J:70081 )

• some areas with four outer hair cell rows rather than three (J:70081)

abnormal inner ear vestibule morphology ( J:70081 )

increased vestibular hair cell number ( J:64679 , J:70081 )

• significant increase of hair cells on sensory epithelium of utricle and saccule (but to a lesser extent) (J:70081)

abnormal utricle morphology ( J:70081 )

abnormal vestibular saccule morphology ( J:70081 )

endocrine/exocrine glands

abnormal bile duct development ( J:87397 )

• truncated conmmon bile duct

• connected to a pancreas like structure

abnormal cystic duct morphology ( J:87397 )

• agenesis of cystic duct

increased solitary pulmonary neuroendocrine cell number ( J:64088 )

• at E13-E18, significantly more CGRP-positive PNECs (including single and clustered PNECs) are observed than in wild-type or heterozygous mutant lungs

absent gallbladder ( J:87397 )

• agenesis of gall bladder

abnormal pancreas morphology ( J:59312 , J:87397 )

• pancreas-like structure develops from common bile duct and contains ectopic endocrine cells in addition to exocrine cells (J:87397)

abnormal exocrine pancreas morphology ( J:59312 )

• exocrine differentiation at E14-15 is normal but with a reduced cytoplasmic/nuclear ratio

• increased apoptosis at E17-19

abnormal pancreas development ( J:59312 )

• no distinct pancreatic buds at E12

• limited pancreatic tissue on opposite sides of duodenum at E14

• fusion of dorsal and ventral evaginations rare

• proliferation of endocrine cells at the expense of pancreatic precursors

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:59312 )

• exocrine differentiation at E14-15 is normal but with a reduced cytoplasmic/nuclear ratio

• increased apoptosis at E17-19

abnormal intestine morphology ( J:59312 )

• precocial endocrine differentiation of intestine

abnormal stomach morphology ( J:59312 )

• precocial endocrine differentiation of stomach

small stomach ( J:59312 )

• development is normal until around E17-19 when it is smaller than normal

liver/biliary system

abnormal bile duct development ( J:87397 )

• truncated conmmon bile duct

• connected to a pancreas like structure

abnormal cystic duct morphology ( J:87397 )

• agenesis of cystic duct

absent gallbladder ( J:87397 )

• agenesis of gall bladder

embryo

decreased embryo size ( J:71074 )

• at E10.5 embryos show signs of growth retardation

abnormal neural tube morphology ( J:30431 , J:71074 )

• 70% of embryos have severe neural tube defects (J:30431)

everted embryonic neuroepithelium ( J:30431 )

• everted neuroepithelium

incomplete rostral neuropore closure ( J:30431 )

• fail to fuse at E9.5

kinked neural tube ( J:30431 )

• occasionally seen around E8.5

growth/size/body

decreased embryo size ( J:71074 )

• at E10.5 embryos show signs of growth retardation

microcephaly ( J:30431 )

decreased body length ( J:64088 )

• at E18, the crown-rump length is significantly shorter than those of wild-type or heterozygous mutant mice

respiratory system

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E12.5 but not at E10.5

decreased club cell number ( J:64088 )

• at E18, the number of Clara cells is significantly decreased in the bronchial and terminal bronchiolar epithelium relative to that in wild-type or heterozygous mice

increased number of pulmonary neuroendocrine bodies ( J:64088 )

• at E13, a few precocious PGP9.5-positive PNEC clusters are seen in the lobar bronchus

• at E18, significantly more airway nodular lesions corresponding to PNEC clusters are observed than in wild-type or heterozygous mutant lungs

small lung ( J:64088 )

• at E18, the longitudinal length of the (left) lung is significantly shorter than those of wild-type or heterozygous mutant mice

cellular

abnormal neuron differentiation ( J:30431 )

• premature neurogenesis as indicated by the appearance of neurofilament and L1(+) cells in the telencephalon at E10.5