All Phenotypes Chd7<Gt(S20-7E1)Sor> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Chd7^{Gt(S20-7E1)Sor}
gene trap S20-7E1, Philippe Soriano
MGI:3707678

Summary

19 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}	129S1.129S4(B6)-Chd7^{Gt(S20-7E1)Sor}	MGI:7493592
hm2	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J	MGI:3708348
hm3	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}	involves: 129S4/SvJaeSor	MGI:4835275
ht4	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	129S1.129S4(B6)-Chd7^{Gt(S20-7E1)Sor}	MGI:7493591
ht5	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	B6;129S-Chd7^{Gt(S20-7E1)Sor}/DmmJ	MGI:7397298
ht6	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	either: (involves: 129S4/SvJae * C57BL/6J) or (involves: 129S1/SvImJ * 129S4/SvJae C57BL/6J)	MGI:3719118
ht7	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S1/SvImJ * 129S4/SvJae	MGI:7496091
ht8	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J	MGI:3708350
ht9	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J * DBA/2J	MGI:7496044
ht10	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S4/SvJaeSor	MGI:4835277
ht11	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S4/SvJaeSor * C57BL/6J	MGI:5807347
ht12	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm	involves: 129 * C57BL/6 * Swiss Webster	MGI:4835274
cn13	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Foxg1^tm1(cre)Skm/Foxg1⁺	involves: 129 * C57BL/6 * Swiss Webster	MGI:4835272
cn14	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Tg(T-cre)1Lwd/0	involves: 129S * C3H * C57BL/6	MGI:7518601
cn15	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Tg(Pax2-cre)1Akg/0	involves: 129S * C57BL/6	MGI:7518554
cn16	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Gt(ROSA)26Sor^{tm6(CAG-ZsGreen1)Hze}/Gt(ROSA)26Sor⁺ Tg(Neurog1-cre)1Jejo/0	involves: 129S * C57BL/6 * SJL/J	MGI:7518675
cx17	Aldh1a3^tm1Gdu/Aldh1a3^tm1Gdu Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6J	MGI:7506323
cx18	Aldh1a3^tm1Gdu/Aldh1a3⁺ Chd7^{Gt(S20-7E1)Sor}/Chd7⁺	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6J	MGI:7506322
cx19	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺ Arb2a^{Tg(Tyr)TpNpin}/Arb2a⁺	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:7429212

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}
Genetic Background	129S1.129S4(B6)-Chd7^{Gt(S20-7E1)Sor}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

taste/olfaction

abnormal nasal placode morphology ( J:174086 )

• olfactory placode size is reduced at E10.5

abnormal olfactory system physiology ( J:174086 )

• E10.5 embryos show a 90% reduction in phospho-histone H3-positive proliferating cells in the developing olfactory placode relative to wild-type controls, and an 80% reduction in H3-positive cells relative to heterozygous embryos

• expression levels of Otx2, Bmp4 and Fgfr1 are significantly decreased in the olfactory placode at E10.5, to a much greater extent than in heterozygous embryos

craniofacial

absent nasal pit ( J:174086 )

• E10.5 embryos appear to lack olfactory pits, suggesting that invagination of the olfactory placode is disrupted

abnormal nasal placode morphology ( J:174086 )

• olfactory placode size is reduced at E10.5

respiratory system

absent nasal pit ( J:174086 )

• E10.5 embryos appear to lack olfactory pits, suggesting that invagination of the olfactory placode is disrupted

abnormal nasal placode morphology ( J:174086 )

• olfactory placode size is reduced at E10.5

cellular

decreased cell proliferation ( J:174086 )

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}
Genetic Background	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

Abnormal development in Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor} mice and delayed turning in Chd7^{Gt(S20-7E1)Sor}/Chd7⁺ embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:119812 )

• no embryos are found after E10.5

hearing/vestibular/ear

abnormal otic vesicle development ( J:119812 )

• at E10.5, the otocyst is thickened

small otic vesicle ( J:119812 )

• at E10.5

embryo

delayed embryo turning ( J:119812 )

• at E10.5

abnormal embryonic neuroepithelium morphology ( J:119812 )

• hypoplastic at E10.5

decreased embryonic neuroepithelium thickness ( J:119812 )

• reduced thickness of the neuroepithelium in the telencephalon, midbrain, and spinal cord

endocrine/exocrine glands

Rathke's pouch hypoplasia ( J:119812 )

• hypoplastic at E10.5

respiratory system

abnormal nasal pit morphology ( J:119812 )

• hypoplasia of the olfactory pits at E10.5

vision/eye

abnormal optic eminence morphology ( J:119812 )

• hypoplasia of the optic eminence at E10.5

limbs/digits/tail

abnormal hindlimb morphology ( J:119812 )

• hypoplasia of the hindlimbs at E10.5

nervous system

abnormal embryonic neuroepithelium morphology ( J:119812 )

• hypoplastic at E10.5

decreased embryonic neuroepithelium thickness ( J:119812 )

• reduced thickness of the neuroepithelium in the telencephalon, midbrain, and spinal cord

Rathke's pouch hypoplasia ( J:119812 )

• hypoplastic at E10.5

abnormal trigeminal ganglion morphology ( J:119812 )

• hypoplastic trigeminal ganglion

craniofacial

abnormal nasal pit morphology ( J:119812 )

• hypoplasia of the olfactory pits at E10.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:119812

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^{Gt(S20-7E1)Sor}
Genetic Background	involves: 129S4/SvJaeSor

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

abnormal ear development ( J:164582 )

• severe reductions in cellular proliferation at E9.5 and E10.5 in both the otic epithelium and the vestibulocochlear ganglion

nervous system

abnormal neuronal precursor proliferation ( J:164582 )

• severe reductions in cellular proliferation at E9.5 and E10.5 in both the otic epithelium and the vestibulocochlear ganglion

abnormal vestibulocochlear ganglion morphology ( J:164582 )

• severely hypoplastic

• severe reductions in cellular proliferation at E9.5 and E10.5 in the vestibulocochlear ganglion

• decrease in the number of apoptotic cells at E9.5

abnormal neuronal precursor cell number ( J:164582 )

• severe reduction in the number of neuroblasts in the otic epithelium and vestibulocochlear ganglion at E9.5, E10.5 and E11.5

cellular

abnormal neuronal precursor proliferation ( J:164582 )

• severe reductions in cellular proliferation at E9.5 and E10.5 in both the otic epithelium and the vestibulocochlear ganglion

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	129S1.129S4(B6)-Chd7^{Gt(S20-7E1)Sor}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

reproductive system

delayed sexual maturation ( J:174086 )

• female mice exhibit delayed puberty

delayed vaginal opening ( J:174086 )

• 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

abnormal estrous cycle ( J:174086 )

• female mice never achieve cyclicity and exhibit highly erratic estrus cycles, with no apparent pattern of timing or duration of cycle stages

delayed estrous cycle ( J:174086 )

• 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

abnormal olfactory epithelium morphology ( J:148116 )

• 10% decrease in the number of basal cells

abnormal olfactory epithelium cilium morphology ( J:148116 )

• cilia markers are consistently patchy indicating regional decreases in cilia components

• patchy distribution is confirmed by SEM

abnormal olfactory sensory neuron morphology ( J:148116 )

• the normal arrangement in parallel stacked columns in the epithelium is lost

decreased olfactory sensory neuron number ( J:148116 )

• 30% reduction in number

abnormal olfactory system physiology ( J:174086 )

• 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

abnormal olfactory epithelium physiology ( J:148116 )

• 50% reduction in proliferating basal cells in adults

abnormal olfactory sensory neuron physiology ( J:148116 )

• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed

impaired olfaction ( J:148116 )

• little to no response to 6 different odorants (amyl acetate, octanal, haptaldehyde, hexanal, eugenol, and carvone) tested by electro-olfactogram

nervous system

abnormal neuron differentiation ( J:174086 )

• GnRH neurogenesis is impaired resulting in reduced GnRH neurons in embryos and adult mice

abnormal olfactory sensory neuron morphology ( J:148116 )

• the normal arrangement in parallel stacked columns in the epithelium is lost

decreased olfactory sensory neuron number ( J:148116 )

• 30% reduction in number

abnormal neurohypophysis median eminence morphology ( J:174086 )

• 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

abnormal pituitary gland physiology ( J:174086 )

• expression levels of Gnrhr (gonadotropin releasing hormone receptor) are significantly reduced in the adult pituitary gland

decreased brain size ( J:148116 )

• decreased length

abnormal telencephalon morphology ( J:148116 )

• decreased length

olfactory bulb hypoplasia ( J:148116 )

• decreased length but not width

• however, intact OMP-positive olfactory bulb glomeruli are present

decreased neuron number ( J:174086 )

• 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

abnormal hypothalamus physiology ( J:174086 )

• expression levels of Gnrh1 (gonadotropin releasing hormone 1) and Otx2 (orthodenticle homeobox 2) are significantly reduced in the adult hypothalamus

abnormal neuron physiology ( J:148116 )

• reduced olfactory interneuron activity

abnormal olfactory sensory neuron physiology ( J:148116 )

• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:174086 , J:174086 , J:174086 )

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 (J:174086) • 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 (J:174086)
N	• female mice show normal serum levels of insulin and leptin relative to wild-type females (J:174086)
N	• 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 (J:174086)

decreased circulating follicle stimulating hormone level ( J:174086 )

• 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

decreased circulating luteinizing hormone level ( J:174086 )

• 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

abnormal olfactory epithelium cilium morphology ( J:148116 )

• cilia markers are consistently patchy indicating regional decreases in cilia components

• patchy distribution is confirmed by SEM

decreased apoptosis ( J:174086 )

• 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%]

abnormal neuron differentiation ( J:174086 )

• GnRH neurogenesis is impaired resulting in reduced GnRH neurons in embryos and adult mice

decreased cell proliferation ( J:174086 )

• 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

endocrine/exocrine gland phenotype ( J:174086 )

N	• mice show normal pituitary gland histology at E10.5, E14.5, E18.5 and in adulthood

abnormal neurohypophysis median eminence morphology ( J:174086 )

• 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

abnormal pituitary gland physiology ( J:174086 )

• expression levels of Gnrhr (gonadotropin releasing hormone receptor) are significantly reduced in the adult pituitary gland

growth/size/body

abnormal olfactory epithelium morphology ( J:148116 )

• 10% decrease in the number of basal cells

abnormal olfactory epithelium cilium morphology ( J:148116 )

• cilia markers are consistently patchy indicating regional decreases in cilia components

• patchy distribution is confirmed by SEM

abnormal olfactory sensory neuron morphology ( J:148116 )

• the normal arrangement in parallel stacked columns in the epithelium is lost

decreased olfactory sensory neuron number ( J:148116 )

• 30% reduction in number

decreased body size ( J:174086 )

• both male and female mice are significantly smaller than wild-type controls

respiratory system

abnormal olfactory epithelium morphology ( J:148116 )

• 10% decrease in the number of basal cells

abnormal olfactory epithelium cilium morphology ( J:148116 )

• cilia markers are consistently patchy indicating regional decreases in cilia components

• patchy distribution is confirmed by SEM

abnormal olfactory sensory neuron morphology ( J:148116 )

• the normal arrangement in parallel stacked columns in the epithelium is lost

decreased olfactory sensory neuron number ( J:148116 )

• 30% reduction in number

abnormal olfactory epithelium physiology ( J:148116 )

• 50% reduction in proliferating basal cells in adults

abnormal olfactory sensory neuron physiology ( J:148116 )

• 4 and 8 weeks after chemical ablation neuronal regeneration is impaired or delayed

craniofacial

abnormal olfactory epithelium morphology ( J:148116 )

• 10% decrease in the number of basal cells

abnormal olfactory epithelium cilium morphology ( J:148116 )

• cilia markers are consistently patchy indicating regional decreases in cilia components

• patchy distribution is confirmed by SEM

abnormal olfactory sensory neuron morphology ( J:148116 )

• the normal arrangement in parallel stacked columns in the epithelium is lost

decreased olfactory sensory neuron number ( J:148116 )

• 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

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	B6;129S-Chd7^{Gt(S20-7E1)Sor}/DmmJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

abnormal semicircular canal morphology ( J:314662 )

• highly penetrant semicircular abnormalities at E14.5 primarily affecting the lateral and posterior canals

vision/eye

decreased retina cone cell number ( J:331474 )

• 40% reduction in the number of cones at P15

short retina cone cell outer segment ( J:331474 )

• reduced length at P15

short retina rod cell outer segment ( J:331474 )

• shorter outer segments at P15

• however, there is no detectable difference in rod density

nervous system

decreased retina cone cell number ( J:331474 )

• 40% reduction in the number of cones at P15

short retina cone cell outer segment ( J:331474 )

• reduced length at P15

short retina rod cell outer segment ( J:331474 )

• shorter outer segments at P15

• however, there is no detectable difference in rod density

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	either: (involves: 129S4/SvJae * C57BL/6J) or (involves: 129S1/SvImJ * 129S4/SvJae C57BL/6J)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

abnormal semicircular canal morphology ( J:123608 )

• at 3 weeks to 11 months, heterozygotes exhibit variable asymmetric defects in posterior and lateral semicircular canals

• in contrast, the anterior semicircular canal and corresponding ampulla and crista remain normal in all heterozygotes

• notably, the utricle and saccule are present in all heterozygous ears, with no differences in shape, hair cell morphology, macular innervation or otoconia relative to wild-type ears

abnormal common crus morphology ( J:123608 )

• at 3 weeks to 11 months, 42 of 50 heterozygous ears display a short common crus

• in the remaning 8 ears (where a distinct PSCC is absent), the area of the common crus either forms a widened bony cavity which contains a patulous common epithelial lumen (6 of 8) or appears as a cavity of normal width, which is associated with a small truncated out-pouching from the superior end in place of a normal PSCC (2 of 8)

abnormal lateral semicircular canal morphology ( J:123608 )

• at 3 weeks to 11 months, all heterozygotes exhibit morphological changes in the lateral canal (LSCC), ranging from a mild alteration in canal shape to total truncation; 14 of 25 heterozygotes display similar, but not identical, defects of the LSCC between ears, and 11 of 25 show different malformation of the LSCC between ears

• although the lateral ampulla is present in most heterozygous ears, 4 of 50 ears show absence of both the ampulla and corresponding cristae; of these four, the LSCC formed a complete but smaller loop in one ear, a bird-beak in another ear, and was truncated in the remaining two ears

• none of the heterozygotes are missing the lateral ampulla in both ears

• variability is noted between different heterozygotes as well as between the right and left ear of the same mouse; of the 13 mice with at least one loop malformation of the LSCC, 5 had bilateral loops, 6 had a bird-beak deformity of the contralateral canal, and 2 had a contralateral LSCC truncation

• variability in loop size is often observed between the ears of mice with bilateral loops; of 12 heterozygotes with at least one LSCC truncation, 7 had bilateral truncations, 3 had a contralateral bird-beak, and 2 had a contralateral loop

• only 2 of the 11 heterozygotes with at least one beak had bilateral beaks; the site and extent of narrowing is variable between the ears of those mice with bilateral peaks

• the extent of LSCC truncation is also variable between ears in some mice

• intra-mouse variability is greater for the beak morphology than for the loop and truncated LSCCs

decreased lateral semicircular canal size ( J:123608 )

• at 3 weeks to 11 months, 19 of 50 heterozygous ears exhibit complete truncation of the non-ampullated end of the LSCC, with canal length varying from >50% of the expected circumference to no more than a tiny bud off the ampulla

• in others, LSCCs appear as complete patent loops of reduced diameter, resulting in a more circular morphology (18 of 50 ears), with significant variability noted in the diameter of the arc of the canal and of the canal lumen

• some LSCCs, display a point of luminal narrowing along their arcs which resembles a bird's beak (13 of 50 ears), most commonly found at the non-ampullated end of the canal

• this constriction is mild in some cases, but in others, the connection between the non-ampullated end and the vestibule is narrow

abnormal posterior semicircular canal morphology ( J:123608 )

• at 3 weeks to 11 months, 42 of 50 heterozygotes display a complete but dysplastic posterior semicircular canal (PSCC) of a more circular "D" shape resulting from a reduced arc diameter, wider canal lumen, and a shorter common crus

• in a few ears, the superior aspect of the PSCC joins the vertical portion of the anterior semicircular canal farther along it course, resulting in an even smaller canal arc

• the size and shape of PSCC is often variable between ears of the same mouse and is bilaterally absent in only 1 of the 7 mice with absence of a distinct PSCC

• however, the posterior crista is always present within the bony posterior ampulla, regardless of whether a distinct PSCC is present

absent posterior semicircular canal ( J:123608 )

• 8 of 50 ears in 7 of 25 heterozygotes lack a distinct PSCC; only one of these 7 mice shows bilateral absence of the PSCC

abnormal crista ampullaris morphology ( J:123608 )

• although the lateral ampulla is present in most heterozygous ears, 4 of 50 ears show absence of both the ampulla and corresponding cristae

• when present, lateral cristae show normal shape, surface morphology and neurofilament staining pattern relative to wild-type cristae; however, the width of lateral cristae is smaller in some ears

• in contrast, all anterior cristae display a normal surface morphology and innervation pattern relative to wild-type cristae

• although posterior cristae are present in all 26 heterozygous ears studied, they show morphological and/or innervation defects

abnormal crista ampullaris neuroepithelium morphology ( J:123608 )

• no lateral sensory epithelium is found in the 4 heterozygous ears lacking a lateral ampulla

• posterior cristae exhibit morphological ranging from a reduction in the surface area of the saddle-shaped sensory epithelium to a flattening of the saddle into a round, patch-like epithelium in all 26 ears studied

• the posterior spetum cruciatum was normal in 3 (of 26) ears and was absent in 2 ears, both of which showed a small patch-like epithelium; the other 21 had a small area devoid of stereocilia at the edge of the sensory epithelium, resembling a rudimentary septum cruciatum, located at the center of the crista

nervous system

abnormal sensory neuron innervation pattern ( J:123608 )

• at 3 weeks to 11 months, heterozygotes display defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in target organs

abnormal vestibular nerve morphology ( J:123608 )

• at 3 weeks to 11 months, the vestibular nerve bundle entering the lateral cristae is visibly smaller in some ears, independent of the degree of severity of lateral canal dysplasia

behavior/neurological

bidirectional circling ( J:123608 )

• 9 of 25 heterozygotes display rapid bi-directional circling during much of their walking hours, although they do stop to eat, rest and mate

• all 9 circling mice display severe bilateral lateral canal defects (truncation or bird-beak defects on each side)

• only 3 mice with such severe bilateral lateral canal defects do not cicle, whereas all 13 mice with the less severe loop defects in at least one ear are non-ciclers

• no cicling mouse is found to have a completely patent lateral semicircular canal

• of the 18 heterozygotes with complete bilateral posterior canals, 6 circle and 12 do not

• of the 6 heterozygotes in which one posterior canal is missing while the contralateral posterior canal is intact, 2 circle and 4 do not

• 6 of 9 circlers and 12 of 18 non-circlers have both posterior canals present

• circling behavior is stronly correlated with lateral canal morphology

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:123608

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S1/SvImJ * 129S4/SvJae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:332873 )

• at 4 and 16 kHz but not at 32 kHz

• however, Wave 1 peak amplitude and peak latency are similar to controls

nervous system

abnormal CNS glial cell morphology ( J:332873 )

• decrease in the number of satellite glial cells but neuron density in the adult spiral ganglion

abnormal vestibulocochlear ganglion morphology ( J:332873 )

• decrease in the number of satellite glial cells but neuron density in the adult spiral ganglion

hypermyelination ( J:332873 )

• increase in myelin thickness on the spiral ganglion neurons

• myelin thickness is increased by 10% in the apex and 15% in the base spiral ganglia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:332873

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

Chd7^{Gt(S20-7E1)Sor}/Chd7⁺ mice exhibit defects of the semicircular canals

mortality/aging

postnatal lethality ( J:119812 )

• reduction in survival at weaning

reproductive system

reduced female fertility ( J:119812 )

• decreased fertility or nurturing behaviors in females that exhibit head-bobbing, circling and hyperactivity

hearing/vestibular/ear

abnormal semicircular canal morphology ( J:119812 )

• variability in the severity of defects in the lateral and posterior semicircular canals is seen between the left and right ears as well as between mice

• however, anterior semicircular canal is normal

absent lateral semicircular canal ( J:119812 )

• in 5 of 8 mice at E16.5

decreased lateral semicircular canal size ( J:119812 )

• severely truncated in 3 of 8 mice at E16.5 with outpouching at the ampulla present and truncation most notably at the nonampullated end

absent posterior semicircular canal ( J:119812 )

• in 4 of 8 mice at E16.5

decreased posterior semicircular canal size ( J:119812 )

• variable severity of truncations of the canal and reduction in size of the ampulla in 4 of 8 mice

behavior/neurological

head bobbing ( J:119812 )

• 24% of F2 offspring exhibit head-bobbing

hyperactivity ( J:119812 )

circling ( J:119812 )

• F1 mice have very few circlers while 24% of F2 offspring exhibit circling

abnormal maternal nurturing ( J:119812 )

• decreased fertility or nurturing behaviors in females that exhibit head-bobbing, circling and hyperactivity

embryo

delayed embryo turning ( J:119812 )

• at E10.5

growth/size/body

decreased body weight ( J:119812 )

• despite similar growth velocities mice weigh less than wild-type

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:119812 )

N	• at E10.5 Rathke's pouch is normal and the pituitary at E12.5-E16.5 is also normal despite the fact that in the human disease, patients have hypogonadotrophic hypogonadism

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:119812

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S1/SvImJ * 129S4/SvJae * C57BL/6J * DBA/2J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

mortality/aging

abnormal induced morbidity/mortality ( J:220430 )

• during exposure to 123 dB broadband noise 7 of 17 mice died

hearing/vestibular/ear

decreased oval window size ( J:220430 )

• generally smaller than in controls

decreased round window size ( J:220430 )

abnormal stapes morphology ( J:220430 )

• fusion of the arch to the dorsal wall of the middle ear cavity

• stapes defects are seen in 5 of 7 mice

abnormal stapes footplate morphology ( J:220430 )

• flattened

• fusion of the footplate to the otic capsule

increased cochlear outer hair cell number ( J:220430 )

• increase in the abundance of supernumerary rows of outer hair cells

abnormal otic capsule morphology ( J:220430 )

• fusion of the stapedial footplate to the otic capsule

increased or absent threshold for auditory brainstem response ( J:220430 )

• increased mean thresholds at 4 kHz and 16 kHz but not at 32 kHz at 5 weeks of age

• increase in thresholds correlates with the absence of a free stapes

absent distortion product otoacoustic emissions ( J:220430 )

• flattened or absent at the mid-frequency range (8, 16, and 24 kHz) in most mice

decreased susceptibility to noise-induced hearing loss ( J:220430 )

• of the 10 mice that survived exposure to 123 dB broadband noise, 6 showed no inner or outer hair cell loss, normal distribution of nerve fibers in the cochlea and no change in hearing thresholds unlike exposure-matched controls

• the other 4 mice showed responses similar to exposure-matched controls

• resistance to noise-induced hearing loss correlates with presence of a fixed stapes

impaired hearing ( J:220430 )

• mild hearing loss at low to mid frequencies

conductive hearing impairment ( J:220430 )

sensorineural hearing impairment ( J:220430 )

craniofacial

decreased oval window size ( J:220430 )

• generally smaller than in controls

decreased round window size ( J:220430 )

abnormal stapes morphology ( J:220430 )

• fusion of the arch to the dorsal wall of the middle ear cavity

• stapes defects are seen in 5 of 7 mice

abnormal stapes footplate morphology ( J:220430 )

• flattened

• fusion of the footplate to the otic capsule

skeleton

decreased oval window size ( J:220430 )

• generally smaller than in controls

decreased round window size ( J:220430 )

abnormal stapes morphology ( J:220430 )

• fusion of the arch to the dorsal wall of the middle ear cavity

• stapes defects are seen in 5 of 7 mice

abnormal stapes footplate morphology ( J:220430 )

• flattened

• fusion of the footplate to the otic capsule

nervous system

increased cochlear outer hair cell number ( J:220430 )

• increase in the abundance of supernumerary rows of outer hair cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:220430

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S4/SvJaeSor

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

abnormal ear development ( J:164582 )

• significantly fewer proliferating cells in the neurogenic domain of the ear at E9.5 and E10.5

nervous system

abnormal neuronal precursor proliferation ( J:164582 )

• decrease in the number of proliferating cells in the vestibulocochlear ganglion at E9.5 but not at E10.5

• significantly fewer proliferating cells in the neurogenic domain of the ear at E9.5 and E10.5

abnormal vestibulocochlear ganglion morphology ( J:164582 )

• decrease in the number of proliferating cells at E9.5 but not at E10.5

abnormal neuronal precursor cell number ( J:164582 )

• decrease in the number of neuroblasts at E10.5 in the ventral otic epithelium and at E9.5 and E10.5 in the vestibulocochlear ganglion

• however, the number of neuroblasts is normal at E11.5

cellular

abnormal neuronal precursor proliferation ( J:164582 )

• decrease in the number of proliferating cells in the vestibulocochlear ganglion at E9.5 but not at E10.5

• significantly fewer proliferating cells in the neurogenic domain of the ear at E9.5 and E10.5

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

reproductive system

abnormal seminiferous tubule morphology ( J:329885 )

• tubules are generally less circular and frequently have irregular linings

vision/eye

coloboma ( J:231044 )

• full penetrance of coloboma, although the extent of involvement within the retina and iris varies

• coloboma is seen at E15.5

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:329885 )

• tubules are generally less circular and frequently have irregular linings

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:231044

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm
Genetic Background	involves: 129 * C57BL/6 * Swiss Webster

Find Mice

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

hearing/vestibular/ear

decreased lateral semicircular canal size ( J:164582 )

• truncated or hypoplastic

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Foxg1^tm1(cre)Skm/Foxg1⁺
Genetic Background	involves: 129 * C57BL/6 * Swiss Webster

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)
Chd7^tm1.1Dmm mutation (1 available); any Chd7 mutation (136 available)
Foxg1^tm1(cre)Skm mutation (2 available); any Foxg1 mutation (28 available)

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

mortality/aging

neonatal lethality, complete penetrance ( J:164582 )

• die within 1 day of birth with no obvious milk in the stomach

hearing/vestibular/ear

abnormal ear development ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

abnormal cochlea morphology ( J:164582 )

• severe defects in cochlear structures

• severely hypoplastic

abnormal cochlear sensory epithelium morphology ( J:310063 )

• undulating appearance in the middle turn of the cochlea

increased cochlear outer hair cell number ( J:310063 )

• supernumerary rows of outer hair cells in the apical cochlea at P1

• occasional extra rows of outer hair cells n the middle turn

• basal turn also shows supernumerary hair cells

decreased cochlea coiling ( J:164582 )

• undercoiled with abnormal twisting at the apex

absent lateral semicircular canal ( J:164582 )

absent posterior semicircular canal ( J:164582 )

abnormal crista ampullaris morphology ( J:164582 )

• absent cristae

decreased superior semicircular canal size ( J:164582 )

• hypoplastic

abnormal inner ear vestibule morphology ( J:164582 )

• severe defects in vestibular structures

absent utricle ( J:164582 )

absent vestibular saccule ( J:164582 )

small endolymphatic duct ( J:164582 )

• hypoplastic

nervous system

abnormal neuronal precursor proliferation ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

increased cochlear outer hair cell number ( J:310063 )

• supernumerary rows of outer hair cells in the apical cochlea at P1

• occasional extra rows of outer hair cells n the middle turn

• basal turn also shows supernumerary hair cells

abnormal vestibulocochlear ganglion morphology ( J:164582 , J:310063 )

• about 1.5 fold smaller at E10.5-E12.5 compared to heterozygous and wild-type controls (J:164582)

• reduction in cellular proliferation at E10.5 in the vestibulocochlear ganglion (J:164582)

• neurites extending away from the hair cells show abnormal looping in the apex at P1 (J:310063)

• abnormal neuritic projections in the middle turn (J:310063)

• disorganized and misrouted neurites in the basal turn (J:310063)

abnormal neuronal precursor cell number ( J:164582 )

• severe reduction in the number of neuroblasts in the otic epithelium and vestibulocochlear ganglion at E9.5, E10.5 and E11.5

craniofacial

short snout ( J:164582 )

• at E12.5

vision/eye

ocular hypertelorism ( J:164582 )

• medially displaced eyes at E12.5

behavior/neurological

abnormal suckling behavior ( J:164582 )

• die within 1 day of birth with no obvious milk in the stomach

cellular

abnormal neuronal precursor proliferation ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

growth/size/body

short snout ( J:164582 )

• at E12.5

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Tg(T-cre)1Lwd/0
Genetic Background	involves: 129S * C3H * C57BL/6

Find Mice

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

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:310063 )

N	• normal vestibular and cochlear morphologies

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Tg(Pax2-cre)1Akg/0
Genetic Background	involves: 129S * C57BL/6

Find Mice

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

hearing/vestibular/ear

abnormal cochlea morphology ( J:310063 )

• severely malformed and hypoplastic

absent lateral semicircular canal ( J:310063 )

absent superior semicircular canal ( J:310063 )

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm Gt(ROSA)26Sor^{tm6(CAG-ZsGreen1)Hze}/Gt(ROSA)26Sor⁺ Tg(Neurog1-cre)1Jejo/0
Genetic Background	involves: 129S * C57BL/6 * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)
Chd7^tm1.1Dmm mutation (1 available); any Chd7 mutation (136 available)
Gt(ROSA)26Sor^{tm6(CAG-ZsGreen1)Hze} mutation (1 available); any Gt(ROSA)26Sor mutation (942 available)
Tg(Neurog1-cre)1Jejo mutation (1 available)

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

nervous system

abnormal vestibulocochlear ganglion morphology ( J:310063 )

• in the apical region of the cochlea aberrant axonal projections that cross, loop, and extend beyond the epithelium are seen

• at P1 total area of the spiral ganglion is reduced

Allelic Composition	Aldh1a3^tm1Gdu/Aldh1a3^tm1Gdu Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aldh1a3^tm1Gdu mutation (1 available); any Aldh1a3 mutation (25 available)
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

hearing/vestibular/ear

abnormal semicircular canal morphology ( J:314662 )

• reduced penetrance of semicircular canal abnormalities compared to mice heterozygous for the Chd7 mutation alone

Allelic Composition	Aldh1a3^tm1Gdu/Aldh1a3⁺ Chd7^{Gt(S20-7E1)Sor}/Chd7⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6J

Find Mice

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

hearing/vestibular/ear

abnormal semicircular canal morphology ( J:314662 )

• semicircular abnormalities at E14.5 similar to mice heterozygous for the Chd7 mutation alone

Allelic Composition	Chd7^{Gt(S20-7E1)Sor}/Chd7⁺ Arb2a^{Tg(Tyr)TpNpin}/Arb2a⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Arb2a^{Tg(Tyr)TpNpin} mutation (0 available); any Arb2a mutation (28 available)
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (136 available)

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:260599 )

• mice exhibit a higher frequency of premature postnatal death

prenatal lethality, incomplete penetrance ( J:260599 )

• lower than expected number of mice at birth

growth/size/body

decreased body size ( J:260599 )

• mice are smaller at weaning age than wild-type mice or either single heterozygote

behavior/neurological

circling ( J:260599 )

reproductive system

sex reversal ( J:260599 )

• mice exhibit a higher frequency of male-to-female sex reversal

vision/eye

abnormal optic fissure closure ( J:260599 )

• E12.5 eyes show a wider choroidal fissure than in either single heterozygote

retina coloboma ( J:260599 )

• coloboma is much more severe than in single heterozygotes

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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