Phenotypes associated with this allele

• Allele Symbol: Hes1^tm1Fgu
• Allele Name: targeted mutation 1, Francois Guillemot
• Allele ID: MGI:2149672
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hes1^tm1Fgu/Hes1^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ	MGI:3713197
hm2	Hes1^tm1Fgu/Hes1^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2172824
ht3	Hes1^tm1Fgu/Hes1^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:4941575
cn4	Emx1^tm1(cre)Ito/Emx1^+ Hes1^tm1Fgu/Hes1^tm1Hojo Hes5^tm1Fgu/Hes5^tm1Fgu	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3713199
cx5	Hes1^tm1Fgu/Hes1^tm1Fgu Hes5^tm1Fgu/Hes5^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ	MGI:3808126
cx6	Hes1^tm1Fgu/Hes1^tm1Fgu Hes3^tm1Kag/Hes3^tm1Kag Hes5^tm1Fgu/Hes5^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3526895
cx7	Hes1^tm1Fgu/Hes1^tm1Fgu Hes5^tm1Fgu/Hes5^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2172828
cx8	Hes1^tm1Fgu/Hes1^+ Hes5^tm1Fgu/Hes5^tm1Fgu	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3617616
cx9	Hes1^tm1Fgu/Hes1^tm1Fgu Hes5^tm1Fgu/Hes5^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3617615
cx10	Hes1^tm1Fgu/Hes1^tm1Fgu Hes3^tm1Kag/Hes3^tm1Kag	involves: C57BL/6 * CBA * ICR	MGI:3526242

Genotype
MGI:3713197

hm1

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

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

endocrine/exocrine glands

abnormal bile duct morphology ( J:151981 )

• mice exhibit biliary agenesis

abnormal bile duct development ( J:151981 )

• the ventral pancreas and biliary primordium do not develop into distinct structures unlike in control mice

abnormal extrahepatic bile duct morphology ( J:151981 )

• hypoplastic

abnormal common bile duct morphology ( J:151981 )

• the common duct is replaced with pancreatic tissue

abnormal pituitary gland development ( J:121843 )

• at E18, here are decreased numbers of pituitary gland progenitor cells compared to wild-type, shown by proliferation assays

pituitary gland hypoplasia ( J:121843 )

• at E18, pituitary gland is hypoplastic but morphologically normal

abnormal pancreas development ( J:151981 )

• the ventral pancreas and biliary primordium do not develop into distinct structures unlike in control mice

nervous system

abnormal pituitary gland development ( J:121843 )

• at E18, here are decreased numbers of pituitary gland progenitor cells compared to wild-type, shown by proliferation assays

pituitary gland hypoplasia ( J:121843 )

• at E18, pituitary gland is hypoplastic but morphologically normal

cellular

abnormal cell differentiation ( J:203419 )

• cultured neural precursor cells have an impaired ability to produce astrocytes

liver/biliary system

abnormal bile duct morphology ( J:151981 )

• mice exhibit biliary agenesis

abnormal bile duct development ( J:151981 )

• the ventral pancreas and biliary primordium do not develop into distinct structures unlike in control mice

abnormal extrahepatic bile duct morphology ( J:151981 )

• hypoplastic

abnormal common bile duct morphology ( J:151981 )

• the common duct is replaced with pancreatic tissue

Genotype
MGI:2172824

hm2

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

mortality/aging

perinatal lethality, complete penetrance ( J:30431 )

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

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

• embryonic death continues to occur

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

Genotype
MGI:4941575

ht3

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

nervous system

increased solitary pulmonary neuroendocrine cell number ( J:64088 )

• at E13-E18, the increase in CGRP-positive PNECs (including single and clustered PNECs) is intermediate between that in wild-type and homozygous mutant lungs

endocrine/exocrine glands

increased solitary pulmonary neuroendocrine cell number ( J:64088 )

• at E13-E18, the increase in CGRP-positive PNECs (including single and clustered PNECs) is intermediate between that in wild-type and homozygous mutant lungs

respiratory system

increased number of pulmonary neuroendocrine bodies ( J:64088 )

• at E13-E18, the increase in PGP9.5-positive PNEC clusters is intermediate between that in wild-type and homozygous mutant lungs

Genotype
MGI:3713199

cn4

• Allelic Composition: Emx1^tm1(cre)Ito/Emx1⁺; Hes1^tm1Fgu/Hes1^tm1Hojo; Hes5^tm1Fgu/Hes5^tm1Fgu
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

endocrine/exocrine glands

abnormal pituitary gland morphology ( J:121843 )

• pituitary gland is sphere-shaped

• gland is composed of round cells only and lacks columnar cells

• cells expressing proopiomelanocortin (POMC) are all round, characteristic of pituitary anterior lobe cells whereas in wild-type, both round and columnar cells (in intermediate lobe) express POMC

increased somatotroph cell number ( J:121843 )

• growth hormone-producing cells are slightly increased in number

abnormal neurohypophysis morphology ( J:121843 )

• at E18, neurohypophysis is lost in mutants, but is formed normally in wild-type and Hes1-null animals

abnormal pituitary infundibular stalk morphology ( J:121843 )

• at E12.5, evagination of the infundibulum is affected compared to control embryos

abnormal pituitary gland development ( J:121843 )

• at E18, there are decreased numbers of pituitary gland progenitor cells compared to wild-type, shown by proliferation assays

• no apoptosis is observed

abnormal pituitary diverticulum morphology ( J:121843 )

• lumen of Rathke's pouch is absent

pituitary gland hypoplasia ( J:121843 )

• at E18, pituitary gland is severely hypoplastic

absent pituitary intermediate lobe ( J:121843 )

• intermediate lobe is absent

nervous system

abnormal pituitary gland morphology ( J:121843 )

• pituitary gland is sphere-shaped

• gland is composed of round cells only and lacks columnar cells

• cells expressing proopiomelanocortin (POMC) are all round, characteristic of pituitary anterior lobe cells whereas in wild-type, both round and columnar cells (in intermediate lobe) express POMC

increased somatotroph cell number ( J:121843 )

• growth hormone-producing cells are slightly increased in number

abnormal neurohypophysis morphology ( J:121843 )

• at E18, neurohypophysis is lost in mutants, but is formed normally in wild-type and Hes1-null animals

abnormal pituitary infundibular stalk morphology ( J:121843 )

• at E12.5, evagination of the infundibulum is affected compared to control embryos

abnormal pituitary gland development ( J:121843 )

• at E18, there are decreased numbers of pituitary gland progenitor cells compared to wild-type, shown by proliferation assays

• no apoptosis is observed

abnormal pituitary diverticulum morphology ( J:121843 )

• lumen of Rathke's pouch is absent

pituitary gland hypoplasia ( J:121843 )

• at E18, pituitary gland is severely hypoplastic

absent pituitary intermediate lobe ( J:121843 )

• intermediate lobe is absent

Genotype
MGI:3808126

cx5

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu; Hes5^tm1Fgu/Hes5^tm1Fgu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal choroid plexus morphology ( J:139170 )

• at E10.5, the choroid plexus of the fourth ventricle is hypoplastic

Genotype
MGI:3526895

cx6

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu; Hes3^tm1Kag/Hes3^tm1Kag; Hes5^tm1Fgu/Hes5^tm1Fgu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

nervous system

premature neuronal precursor differentiation ( J:94391 )

• at E8.5 many differentiated neurons have already formed unlike in Hes1, Hes5 double mutants where premature differentiation is not seen until E9.5

• at E9.5 almost all cells are neurons in the ventral spinal cord and at E10.0 virtually all radial glial cells have differentiated

cellular

premature neuronal precursor differentiation ( J:94391 )

• at E8.5 many differentiated neurons have already formed unlike in Hes1, Hes5 double mutants where premature differentiation is not seen until E9.5

• at E9.5 almost all cells are neurons in the ventral spinal cord and at E10.0 virtually all radial glial cells have differentiated

Genotype
MGI:2172828

cx7

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu; Hes5^tm1Fgu/Hes5^tm1Fgu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:94391 )

• homozygous double mutants die by E11

nervous system

premature neuronal precursor differentiation ( J:94391 )

• at E9.5 and E10.5 radial glial cells prematurely differentiate into neurons resulting in failure of later born cells (oligodendrocytes, astrocytes, and ependymal cells) to be generated

• at E9.5 and E10.5 prematurely differentiated neurons are found in the regions where the optic vesicles should develop

abnormal neural tube morphology ( J:62024 , J:94391 )

• neural tube defects in 71.2% of embryos (J:62024)

• at E10.5 the cells of the neural tube are disorganized with many cells scattered across the lumen rather in contrast to the radial morphology seen in wild-type mice (J:94391)

• also at E10.5 the outer boundary of the neural tube is irregular and ambiguous (J:94391)

abnormal brain development ( J:94391 )

abnormal forebrain morphology ( J:94391 )

• the forebrain monotonous tube

abnormal ependyma morphology ( J:94391 )

• ependymal cells are absent

abnormal CNS glial cell morphology ( J:94391 )

abnormal astrocyte morphology ( J:94391 )

• astrocytes are absent

absent oligodendrocytes ( J:94391 )

• oligodendrocytes are absent

abnormal embryonic/fetal subventricular zone morphology ( J:94391 )

• the ganglionic eminences are not properly formed due to premature neuronal differentiation

neuron hypertrophy ( J:54662 )

• even greater neuron density in double homozygotes

abnormal dorsal root ganglion morphology ( J:94391 )

• neurons of the spinal cord and dorsal root ganglia are intermingled

abnormal spinal cord morphology ( J:94391 )

• the basal lamina is missing from the ventral spinal cord and neurons of the spinal cord and dorsal root ganglia are intermingled

vision/eye

absent optic vesicle ( J:94391 )

• at E9.5 and E10.5 the optic vesicles are absent; instead, differentiated neurons are found in the region that would normally become the optic vesicle

taste/olfaction

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E10.5

growth/size/body

decreased embryo size ( J:54662 )

embryo

decreased embryo size ( J:54662 )

abnormal neural tube morphology ( J:62024 , J:94391 )

• neural tube defects in 71.2% of embryos (J:62024)

• at E10.5 the cells of the neural tube are disorganized with many cells scattered across the lumen rather in contrast to the radial morphology seen in wild-type mice (J:94391)

• also at E10.5 the outer boundary of the neural tube is irregular and ambiguous (J:94391)

respiratory system

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E10.5

craniofacial

abnormal nasal placode morphology ( J:62024 )

• increased numbers of neurons in olfactory placodes at E10.5

cellular

premature neuronal precursor differentiation ( J:94391 )

• at E9.5 and E10.5 radial glial cells prematurely differentiate into neurons resulting in failure of later born cells (oligodendrocytes, astrocytes, and ependymal cells) to be generated

• at E9.5 and E10.5 prematurely differentiated neurons are found in the regions where the optic vesicles should develop

Genotype
MGI:3617616

cx8

• Allelic Composition: Hes1^tm1Fgu/Hes1⁺; Hes5^tm1Fgu/Hes5^tm1Fgu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

hearing/vestibular/ear

increased cochlear outer hair cell number ( J:70081 )

• significantly increased outer hair cell numbers relative to homozygotes or controls

nervous system

increased cochlear outer hair cell number ( J:70081 )

• significantly increased outer hair cell numbers relative to homozygotes or controls

Genotype
MGI:3617615

cx9

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu; Hes5^tm1Fgu/Hes5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

hearing/vestibular/ear

increased cochlear inner hair cell number ( J:70081 )

• significantly increased inner hair cell numbers relative to homozygotes or controls

nervous system

increased cochlear inner hair cell number ( J:70081 )

• significantly increased inner hair cell numbers relative to homozygotes or controls

Genotype
MGI:3526242

cx10

• Allelic Composition: Hes1^tm1Fgu/Hes1^tm1Fgu; Hes3^tm1Kag/Hes3^tm1Kag
• Genetic Background: involves: C57BL/6 * CBA * ICR

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:71074 )

• most homozygous double mutants survive to E10.5 but die by E15.5

growth/size/body

embryonic growth retardation ( J:71074 )

• at E10.5 embryos show signs of growth retardation

nervous system

premature neuronal precursor differentiation ( J:71074 )

• at E10.5 more neurons are generated prematurely however many neuronal precursors remain

abnormal neural tube morphology ( J:71074 )

• all double homozygotes had some type of neural tube defect

abnormal brain development ( J:71074 )

abnormal midbrain-hindbrain boundary morphology ( J:71074 )

• at E10.5 the isthmic organizer is prematurely lost as a result of premature differentiation of neuronal precursors

abnormal midbrain morphology ( J:71074 )

• the oculomotor and trochlear motor nuclei are absent at E10.5 and E12.5

abnormal oculomotor nucleus morphology ( J:71074 )

• the oculomotor nuclei are absent at E10.5 and E12.5

abnormal locus ceruleus morphology ( J:71074 )

• the locus ceruleus is absent at E10.5

exencephaly ( J:71074 )

• some embryos had exencephaly of the whole brain while in others the defect was confined to the midbrain-hindbrain region

abnormal dopaminergic neuron morphology ( J:71074 )

• dopaminergic neurons are absent at E11.5

absent oculomotor nerve ( J:71074 )

• at E12.5 the oculomoter nerve is absent

absent trochlear nerve ( J:71074 )

• at E12.5 the trochlear nerve is absent

embryo

embryonic growth retardation ( J:71074 )

• at E10.5 embryos show signs of growth retardation

abnormal neural tube morphology ( J:71074 )

• all double homozygotes had some type of neural tube defect

cellular

premature neuronal precursor differentiation ( J:71074 )

• at E10.5 more neurons are generated prematurely however many neuronal precursors remain