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

Phenotypes associated with this allele

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 (138 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 (138 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 (138 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

♀	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

decreased gonadotropin-releasing hormone 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 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

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 )

• 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

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

decreased gonadotropin-releasing hormone 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 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 (138 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 (138 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

abnormal inner ear vestibular 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

nervous system

abnormal inner ear vestibular 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 (138 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 (138 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 (138 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 (138 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 (138 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 (138 available)
Chd7^tm1.1Dmm mutation (1 available); any Chd7 mutation (138 available)
Foxg1^tm1(cre)Skm mutation (2 available); any Foxg1 mutation (29 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 (138 available)
Chd7^tm1.1Dmm mutation (1 available); any Chd7 mutation (138 available)
Gt(ROSA)26Sor^{tm6(CAG-ZsGreen1)Hze} mutation (1 available); any Gt(ROSA)26Sor mutation (1006 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 (26 available)
Chd7^{Gt(S20-7E1)Sor} mutation (1 available); any Chd7 mutation (138 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 (138 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

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