Phenotypes associated with this allele

• Allele Symbol: Nog^tm1Amc
• Allele Name: targeted mutation 1, Andrew P McMahon
• Allele ID: MGI:1862000
• Summary: 27 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nog^tm1Amc/Nog^tm1Amc	B6.129S1-Nog^tm1Amc	MGI:3624833
hm2	Nog^tm1Amc/Nog^tm1Amc	D1.129S1-Nog^tm1Amc	MGI:3624830
hm3	Nog^tm1Amc/Nog^tm1Amc	either: 129/Sv or (involves: 129S1/Sv * C57BL/6J)	MGI:2672116
hm4	Nog^tm1Amc/Nog^tm1Amc	either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)	MGI:3819135
hm5	Nog^tm1Amc/Nog^tm1Amc	either: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3819175
hm6	Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv	MGI:3723136
hm7	Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * C57BL/6J * FVB/N	MGI:4430832
hm8	Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * C57BL/6J * ICR	MGI:3819380
hm9	Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * CD-1	MGI:3624837
hm10	Nog^tm1Amc/Nog^tm1Amc	involves: C57BL/6	MGI:3817999
ht11	Nog^tm1Amc/Nog^+	B6.129S1-Nog^tm1Amc	MGI:3624836
ht12	Nog^tm1Amc/Nog^+	D1.129S1-Nog^tm1Amc	MGI:3624831
ht13	Nog^tm1Amc/Nog^+	involves: 129S1/Sv * C57BL/6J * ICR	MGI:3819381
ht14	Nog^tm1Amc/Nog^+	involves: 129S1/Sv * CD-1	MGI:3624838
ht15	Nog^tm1Amc/Nog^+	involves: C57BL/6J * FVB	MGI:3819764
cx16	Bmp7^tm1Kry/Bmp7^tm1Kry Nog^tm1Amc/Nog^tm1Amc	either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)	MGI:3819143
cx17	Nbl1^tm1Rmh/Nbl1^tm1Rmh Nog^tm1Amc/Nog^tm1Amc	involves: 129P2/OlaHsd * 129S1/Sv * 129S6/SvEvTac	MGI:3034044
cx18	Bmp4^tm2Blh/Bmp4^+ Nog^tm1Amc/Nog^+	involves: 129S1/Sv * 129S6/SvEvTac	MGI:3818001
cx19	Bmp4^tm2Blh/Bmp4^+ Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129S6/SvEvTac	MGI:3818000
cx20	Cer1^tm1Belo/Cer1^tm1Belo Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129X1/SvJ	MGI:3723131
cx21	Chrd^tm1Emdr/Chrd^tm1Emdr Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:2662585
cx22	Chrd^tm1Emdr/Chrd^tm1Emdr Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:2173453
cx23	Nodal^tm1Rob/Nodal^+ Nog^tm1Amc/Nog^tm1Amc	involves: 129S/SvEv * 129S1/Sv	MGI:4819102
cx24	Nog^tm1Amc/Nog^tm1Amc Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv	MGI:4819098
cx25	Nog^tm1Amc/Nog^tm1Amc Smad3^tm1Xfw/Smad3^tm1Xfw	involves: 129/Sv * 129S1/Sv	MGI:4819101
cx26	Nog^tm1Amc/Nog^+ Smad3^tm1Xfw/Smad3^tm1Xfw	involves: 129/Sv * 129S1/Sv	MGI:4819100
cx27	Nog^tm1Amc/Nog^+ Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv	MGI:4819099

Genotype
MGI:3624833

hm1

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: B6.129S1-Nog^tm1Amc

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:108573 )

• Background Sensitivity: embryo death before E14.5 on a B6.129S1 background

embryo

small limb buds ( J:108573 )

• Background Sensitivity: reduction in limb buds is seen on the C57BL/6 background but not so much on a CD-1 background

hearing/vestibular/ear

abnormal incus morphology ( J:132023 )

• at E17.5 incus is malformed

abnormal malleus morphology ( J:132023 )

• at E17.5 malleus is malformed

fusion of middle ear ossicles ( J:132023 )

• at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

craniofacial

abnormal incus morphology ( J:132023 )

• at E17.5 incus is malformed

abnormal malleus morphology ( J:132023 )

• at E17.5 malleus is malformed

fusion of middle ear ossicles ( J:132023 )

• at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

limbs/digits/tail

small limb buds ( J:108573 )

• Background Sensitivity: reduction in limb buds is seen on the C57BL/6 background but not so much on a CD-1 background

skeleton

abnormal incus morphology ( J:132023 )

• at E17.5 incus is malformed

abnormal malleus morphology ( J:132023 )

• at E17.5 malleus is malformed

fusion of middle ear ossicles ( J:132023 )

• at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

Genotype
MGI:3624830

hm2

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: D1.129S1-Nog^tm1Amc

mortality/aging

perinatal lethality ( J:108573 )

nervous system

exencephaly ( J:108573 )

• 25% penetrance, lower than on a CD-1 background

Genotype
MGI:2672116

hm3

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: either: 129/Sv or (involves: 129S1/Sv * C57BL/6J)

mortality/aging

perinatal lethality, complete penetrance ( J:47724 )

nervous system

abnormal neural tube morphology ( J:47724 )

• reduced in size

incomplete rostral neuropore closure ( J:47724 )

• Background Sensitivity: on a 129/Sv background the brain fails to close between the diencephalons and myelencephalon, sometimes remaining open all the way to the caudal limit

• Background Sensitivity: neural folds flatten at the 8-9 somite stage on the 129/Sv background

• Background Sensitivity: on a mixed background the brain closes

abnormal spinal cord morphology ( J:47724 )

• becomes kinked on both backgrounds

embryo

decreased embryo size ( J:47724 )

abnormal neural tube morphology ( J:47724 )

• reduced in size

incomplete rostral neuropore closure ( J:47724 )

• Background Sensitivity: on a 129/Sv background the brain fails to close between the diencephalons and myelencephalon, sometimes remaining open all the way to the caudal limit

• Background Sensitivity: neural folds flatten at the 8-9 somite stage on the 129/Sv background

• Background Sensitivity: on a mixed background the brain closes

abnormal notochord morphology ( J:47724 )

• occasional side branching and buckling at E10.5

abnormal somite development ( J:47724 )

abnormal rostral-caudal patterning of the somites ( J:47724 )

• abnormalities become increasingly severe in a caudal direction

decreased somite size ( J:47724 )

• reduced

skeleton

abnormal axial skeleton morphology ( J:47724 )

• shortened axis between fore and hind limbs

vision/eye

abnormal eye development ( J:47724 )

• perturbed

hearing/vestibular/ear

abnormal ear development ( J:47724 )

• perturbed

limbs/digits/tail

short limbs ( J:47724 )

• broad club shaped limbs

vestigial tail ( J:47724 )

• reduced at E12.5, absent later

growth/size/body

decreased embryo size ( J:47724 )

integument

abnormal hair follicle development ( J:59676 )

• significantly reduced numbers of hair follicles and fewer reach an advanced stage of morphogenesis than normal

• more apoptosis in hair placodes

Genotype
MGI:3819135

hm4

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)

embryo

abnormal neural tube morphology ( J:118341 )

incomplete rostral neuropore closure ( J:118341 )

• at E11.5 embryos show open brain phenotype

open neural tube ( J:118341 )

• at E11.5 caudal neural tube is open

abnormal notochord morphology ( J:118341 )

• abnormal at E8.5 and E9, indicating delayed detachment from dorsal foregut endoderm; appears hypertrophic compared to wild-type at E9

• no clear boundary between notochord and endoderm is detected at E8.5

• at E9.5, notochord has lateral branches close to or tethered to dorsal foregut in contrast to wild-type notochord

• increased apoptotic cell numbers are seen at E9.5-E9.75

• non-notochordal cells are observed within the notochord at E9.0

digestive/alimentary system

abnormal esophagus development ( J:118341 )

• at E10.5-11.5 most mutants display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF); some embryos show milder phenotype indicative of esophageal stenosis

abnormal foregut morphology ( J:118341 )

• at E9.5, reduction in dorsoventral diameter of the foregut is observed; dorsal foregut endoderm is reduced in mutant embryos

• loosening or loss of dorsal foregut cells is consistently observed at E9; endodermal cells show basement membrane disruption

esophageal atresia ( J:118341 )

• at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF)

esophagus stenosis ( J:118341 )

• severe narrowing of the esophagus is seen by E9.5

tracheoesophageal fistula ( J:118341 )

• at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF) with the upper esophagus ending in a blind pouch and the lower esophagus connects to the trachea via a fistula

nervous system

abnormal neural tube morphology ( J:118341 )

incomplete rostral neuropore closure ( J:118341 )

• at E11.5 embryos show open brain phenotype

open neural tube ( J:118341 )

• at E11.5 caudal neural tube is open

respiratory system

tracheoesophageal fistula ( J:118341 )

• at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF) with the upper esophagus ending in a blind pouch and the lower esophagus connects to the trachea via a fistula

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
esophageal atresia/tracheoesophageal fistula		DOID:0080171	OMIM:189960	J:118341

Genotype
MGI:3819175

hm5

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: either: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

endocrine/exocrine glands

absent adenohypophysis ( J:121318 )

• in embryos with elongated, rostrally-positioned Rathke's pouch, developed anterior lobe is absent

absent pituitary infundibular stalk ( J:121318 )

• morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5

abnormal pituitary gland development ( J:121318 )

• Rathke's pouch and anterior lobe development are severely affected

• some cell specification appears to occur in pituitary tissue

• secondary pituitary tissue is found in some embryos examined at E11.5-14.5 with percentage of affected embryos decreasing when examined at later time point (E15.5-18.5)

abnormal Rathke's pouch apoptosis ( J:121318 )

• domain of apoptosis normally observed on ventral side of pouch is absent in mutants at E10.5 and E11.5; apoptotic cells are not observed in mutants that do not achieve separation of Rathke's pouch

abnormal Rathke's pouch development ( J:121318 )

• severely malformed at E10.5 with multiple invaginations within oral ectoderm; some embryos show duplication of Rathke's pouch with the two invaginations widely spaced or arising adjacent to each other

• commonly, Rathke's pouch is elongated and extend more rostrally than in wild-type; eventually cartilage plate surrounds mutant pituitary tissue

absent Rathke's pouch ( J:121318 )

• about 14% of embryos don't appear to have a Rathke's pouch at E12.5

absent pituitary gland ( J:121318 )

• in some embryos an identifiable pituitary is not found at E12.5-16.5; normal position of pituitary is filled with mesenchyme in these embryos

abnormal pituitary gland physiology ( J:121318 )

• all normal pituitary hormones are detected in primary anterior lobe of mutants but levels are variable, dependent on number of terminally differentiated cells

nervous system

abnormal neural tube morphology ( J:121318 )

• severe neural tube defect is occasionally observed

abnormal pituitary gland physiology ( J:121318 )

• all normal pituitary hormones are detected in primary anterior lobe of mutants but levels are variable, dependent on number of terminally differentiated cells

abnormal diencephalon morphology ( J:121318 )

• ventral diencephalon displays abnormalities

• a large domain of cell death is observed in ventral diencephalon of mutants but not in wild-type

• thickening of neuroepithelium in ventral diencephalon rostral to Rathke's pouch is decreased or absent in contrast to wild-type embryos

absent adenohypophysis ( J:121318 )

• in embryos with elongated, rostrally-positioned Rathke's pouch, developed anterior lobe is absent

absent pituitary infundibular stalk ( J:121318 )

• morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5

abnormal pituitary gland development ( J:121318 )

• Rathke's pouch and anterior lobe development are severely affected

• some cell specification appears to occur in pituitary tissue

• secondary pituitary tissue is found in some embryos examined at E11.5-14.5 with percentage of affected embryos decreasing when examined at later time point (E15.5-18.5)

abnormal Rathke's pouch apoptosis ( J:121318 )

• domain of apoptosis normally observed on ventral side of pouch is absent in mutants at E10.5 and E11.5; apoptotic cells are not observed in mutants that do not achieve separation of Rathke's pouch

abnormal Rathke's pouch development ( J:121318 )

• severely malformed at E10.5 with multiple invaginations within oral ectoderm; some embryos show duplication of Rathke's pouch with the two invaginations widely spaced or arising adjacent to each other

• commonly, Rathke's pouch is elongated and extend more rostrally than in wild-type; eventually cartilage plate surrounds mutant pituitary tissue

absent Rathke's pouch ( J:121318 )

• about 14% of embryos don't appear to have a Rathke's pouch at E12.5

absent pituitary gland ( J:121318 )

• in some embryos an identifiable pituitary is not found at E12.5-16.5; normal position of pituitary is filled with mesenchyme in these embryos

embryo

abnormal neural tube morphology ( J:121318 )

• severe neural tube defect is occasionally observed

growth/size/body

abnormal head morphology ( J:121318 )

• with severe neural tube defect gross head morphology is altered, being split down anterior midline at E15.5

Genotype
MGI:3723136

hm6

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv

mortality/aging

perinatal lethality, complete penetrance ( J:74136 , J:110617 )

• time of death not specified (J:74136)

• mice all die perinatally (J:110617)

nervous system

abnormal neural plate morphology ( J:110617 )

• neural plate shows furrows and kinks in open cranial portion and closed spinal portion

abnormal neural tube morphology ( J:110617 )

• neural tube at level of forelimbs is mildly affected

• between the limbs, flattened neural mass beneath edematous tissue replaces neural tube

• all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs)

• defective neurulation is detected at E9.0

• at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured

abnormal neural tube closure ( J:74136 , J:110617 )

• abnormalities in neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon (J:74136)

• walls of neural tube remain relatively flat or convex rather than bending to form concave walls (J:110617)

incomplete rostral neuropore closure ( J:110617 )

• all but most rostral portion of neural tube remains splayed open with no surface ectoderm covering open neural tissue at E9.0

open neural tube ( J:74136 )

spina bifida occulta ( J:110617 )

• all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent

• vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

• stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb

kinked neural tube ( J:110617 )

• observed in embryos at E8 or E9

wavy neural tube ( J:110617 )

• observed in embryos at E8 or E9

exencephaly ( J:74136 , J:110617 )

• in mutants where the frontal, parietal and interparietal bones are absent, the brain is exposed at birth (J:74136)

• midbrain and hindbrain regions are directly exposed to extraembryonic environment (J:110617)

• large convoluted mass of brain tissue protrudes from head (J:110617)

• Background Sensitivity: exencephaly is completely penetrant on 129/Sv background, but is almost never observed on C57BL/6 background and is variably observed on mixed or outbred backgrounds (J:110617)

abnormal spinal cord morphology ( J:110617 )

• by E14, spinal cord is splayed open and dysmorphic in lumbar region, but remains closed at forelimb level

skeleton

abnormal axial skeleton morphology ( J:110617 )

• all mutants show overgrowth and fusion of axial skeletal elements at birth

• at E14, axial skeleton supporting the spinal cord is malformed and deficient in lumbar region of embryo

abnormal basicranium morphology ( J:74136 )

• fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology ( J:74136 )

• frontal bone is loose or absent

abnormal interparietal bone morphology ( J:74136 )

• interparietal bone is loose or absent

abnormal occipital bone morphology ( J:74136 )

• occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology ( J:74136 )

• parietal bone is loose or absent

abnormal vertebral arch morphology ( J:110617 )

• vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

spina bifida occulta ( J:110617 )

• all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent

• vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

• stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb

absent vertebral arch ( J:110617 )

• caudal to forelimb, dorsal neural arches are absent

limbs/digits/tail

short limbs ( J:74136 )

• truncated limbs

absent tail ( J:74136 )

respiratory system

abnormal lung morphology ( J:83697 )

• at E15.5 all mice have abnormal lungs with malformed and truncated lobes

abnormal lung development ( J:83697 )

• blind-ended ectopic buds or diverticulum emerging near the junction of the main bronchi are present in 31% of embryos

abnormal right lung morphology ( J:83697 )

• fusions of the right lobes are seen in 78% of embryos

craniofacial

abnormal basicranium morphology ( J:74136 )

• fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology ( J:74136 )

• frontal bone is loose or absent

abnormal interparietal bone morphology ( J:74136 )

• interparietal bone is loose or absent

abnormal occipital bone morphology ( J:74136 )

• occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology ( J:74136 )

• parietal bone is loose or absent

cellular

increased apoptosis ( J:110617 )

embryo

abnormal neural plate morphology ( J:110617 )

• neural plate shows furrows and kinks in open cranial portion and closed spinal portion

abnormal neural tube morphology ( J:110617 )

• neural tube at level of forelimbs is mildly affected

• between the limbs, flattened neural mass beneath edematous tissue replaces neural tube

• all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs)

• defective neurulation is detected at E9.0

• at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured

abnormal neural tube closure ( J:74136 , J:110617 )

• abnormalities in neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon (J:74136)

• walls of neural tube remain relatively flat or convex rather than bending to form concave walls (J:110617)

incomplete rostral neuropore closure ( J:110617 )

• all but most rostral portion of neural tube remains splayed open with no surface ectoderm covering open neural tissue at E9.0

open neural tube ( J:74136 )

spina bifida occulta ( J:110617 )

• all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent

• vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

• stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb

kinked neural tube ( J:110617 )

• observed in embryos at E8 or E9

wavy neural tube ( J:110617 )

• observed in embryos at E8 or E9

abnormal somite development ( J:110617 )

• somite differentiation is disrupted in lumbar region of embryos at E9-10

Genotype
MGI:4430832

hm7

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * C57BL/6J * FVB/N

hearing/vestibular/ear

abnormal cochlea morphology ( J:156945 )

• length of cochlea is shorter by 35% compared to heterozygous controls at E18.5

increased cochlear inner hair cell number ( J:156945 )

• cochleae have occasional extra inner hair cells (IHCs) at the base of the cochlea, and two rows of IHCs in the middle and apical turns instead of a single row as in controls

• increase in IHCs is observed in any given region but is more pronounced in apical and middle turns

• total estimated IHC number based on entire length of cochlear duct is increased by 11%

increased cochlear outer hair cell number ( J:156945 )

• an extra row of outer hair cells (OHCs) is observed in the apical and middle turns of the cochleae; numbers increase significantly throughout each turn

• however, total estimated OHC number based on entire length of cochlear duct is decreased by 24% compared to heterozygous controls

decreased cochlea coiling ( J:156945 )

• cochleae of controls show 1.75 turns compared to only 1 turn in mutants

nervous system

increased cochlear inner hair cell number ( J:156945 )

• cochleae have occasional extra inner hair cells (IHCs) at the base of the cochlea, and two rows of IHCs in the middle and apical turns instead of a single row as in controls

• increase in IHCs is observed in any given region but is more pronounced in apical and middle turns

• total estimated IHC number based on entire length of cochlear duct is increased by 11%

increased cochlear outer hair cell number ( J:156945 )

• an extra row of outer hair cells (OHCs) is observed in the apical and middle turns of the cochleae; numbers increase significantly throughout each turn

• however, total estimated OHC number based on entire length of cochlear duct is decreased by 24% compared to heterozygous controls

Genotype
MGI:3819380

hm8

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * C57BL/6J * ICR

embryo

abnormal primitive urogenital sinus morphology ( J:130204 )

• UGS is smaller at E17 in males

abnormal septation of the cloaca ( J:130204 )

• incomplete separation of the hindgut from the urogenital sinus (UGS) is observed in some embryos

• at E17 males have a fistulous connection between hindgut and dorsal surface of UGS; females show similar defects at E17

• at E14 ventral mesenchymal cell density of UGS is reduced relative to E14 wild-type embryos indicating defective development of the ventral mesenchyme pad; this reduced cell density occurs along with decreased epithelial cell proliferation in the ventral UGS

• at P1 this is observed as reduction in ventral mesenchyme pad thickness and density

reproductive system

abnormal male reproductive system morphology ( J:130204 )

♂ • dorsal ridges are absent or reduced in size; dorsal sulcus is missing and ejaculatory duct connection is exposed

absent bulbourethral gland ( J:130204 )

♂ • some males show agenesis of the bulbourethral gland

abnormal prostate gland morphology ( J:130204 )

♂ • dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos

abnormal prostate gland development ( J:130204 )

♂ • in developing embryos the ventral prostate (VP) bud is absent

♂ • in developing prostate the coagulating gland bud is absent

cryptorchism ( J:130204 )

♂ • varying degrees of cryptorchism ranging from high intra-abdominal position to complete descent

renal/urinary system

pelvic kidney ( J:130204 )

• occasionally an ectopic kidney is observed in the pelvic cavity

abnormal urethra morphology ( J:130204 )

• some males exhibit agenesis of the membranous (pelvic) urethra while others develop a preursor urethral epithelial tube

• angle between bladder neck and urethra in urogenital sinus (UGS) is much larger than the approximate 90 degrees seen in wild-type embryos

abnormal urinary system development ( J:130204 )

digestive/alimentary system

anal atresia ( J:130204 )

• fistulous connection between hindgut and dorsal UGS surface is typically associated with anal atresia in males and females

endocrine/exocrine glands

absent bulbourethral gland ( J:130204 )

♂ • some males show agenesis of the bulbourethral gland

abnormal prostate gland morphology ( J:130204 )

♂ • dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos

abnormal prostate gland development ( J:130204 )

♂ • in developing embryos the ventral prostate (VP) bud is absent

♂ • in developing prostate the coagulating gland bud is absent

cryptorchism ( J:130204 )

♂ • varying degrees of cryptorchism ranging from high intra-abdominal position to complete descent

limbs/digits/tail

absent tail ( J:130204 )

• some embryos exhibit agenesis of the tail

Genotype
MGI:3624837

hm9

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * CD-1

mortality/aging

perinatal lethality ( J:108573 )

skeleton

fused synovial joints ( J:108573 )

• elbow fusion

abnormal bone mineralization ( J:108573 )

• highly variable throughout the skeleton but characteristic for each region

limbs/digits/tail

abnormal limb morphology ( J:108573 )

• newbrons exhibit stubby limbs

abnormal limb bud morphology ( J:108573 )

• Background Sensitivity: limb bud phenotype is much less pronounced, such that they almost appear normal, in the CD-1 background compared to the C57BL/6 background

vestigial tail ( J:108573 )

• degeneration of the tail structure is seen at E12.5

homeostasis/metabolism

edema ( J:108573 )

• observed at E14.5

muscle

abnormal muscle morphology ( J:108573 )

• reduced muscle tissue in newborns

abnormal muscle fiber morphology ( J:108573 )

• myofibers in loose structures rather than tightly packed

cardiovascular system

hematoma ( J:108573 )

• a large hematoma is often seen in the degenerating tail at E12.5 and by E14.5, hematomas in other parts of the body are seen

nervous system

exencephaly ( J:108573 )

• Background Sensitivity: 60% penetrance, higher than on a DBA/1 background

growth/size/body

decreased fetal size ( J:108573 )

• shorter along the rostral-caudal axis

embryo

abnormal limb bud morphology ( J:108573 )

• Background Sensitivity: limb bud phenotype is much less pronounced, such that they almost appear normal, in the CD-1 background compared to the C57BL/6 background

integument

abnormal hair follicle development ( J:108573 )

• rudimentary hair follicles at E18.5

Genotype
MGI:3817999

hm10

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:110617 )

• mice all die perinatally

nervous system

abnormal neural tube morphology ( J:110617 )

• all homozygotes display spinal neural tube defects

exencephaly ( J:110617 )

• never observed on C57BL/6 inbred background

skeleton

abnormal skeleton morphology ( J:110617 )

• all homozygotes display severe skeletal malformations

craniofacial

abnormal craniofacial morphology ( J:110617 )

• some mutants show severe craniofacial truncations

short face ( J:110617 )

• some mutants show mild facial truncations

embryo

abnormal neural tube morphology ( J:110617 )

• all homozygotes display spinal neural tube defects

growth/size/body

short face ( J:110617 )

• some mutants show mild facial truncations

Genotype
MGI:3624836

ht11

• Allelic Composition: Nog^tm1Amc/Nog⁺
• Genetic Background: B6.129S1-Nog^tm1Amc

skeleton

abnormal rib morphology ( J:108573 )

small thoracic cage ( J:108573 )

• reduced rib cage due to malformed ribs

fused synovial joints ( J:108573 )

• carpal and tarsal fusions in 100% of mice in all backgrounds

• no additional fusions throughout life

limbs/digits/tail

kinked tail ( J:108573 )

• in embryos at E14.5

Genotype
MGI:3624831

ht12

• Allelic Composition: Nog^tm1Amc/Nog⁺
• Genetic Background: D1.129S1-Nog^tm1Amc

skeleton

abnormal styloid process morphology ( J:132023 )

• in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally

abnormal middle ear ossicle morphology ( J:132023 )

• mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium

• fragment is located where stapedius muscle is connected to temporal bone in wild-type ears

• no extra bone fragment associated with the malleus or incus was observed

• mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected ears

• bone bridges are not observed in unaffected or mildly affected ears

abnormal stapes morphology ( J:132023 )

• in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally

abnormal rib morphology ( J:108573 )

small thoracic cage ( J:108573 )

• reduced rib cage due to malformed ribs

fused synovial joints ( J:108573 )

• carpal and tarsal fusions in 100% of mice in all backgrounds

• no additional fusions throughout life

limbs/digits/tail

kinked tail ( J:108573 )

• in embryos at E14.5

craniofacial

abnormal styloid process morphology ( J:132023 )

• in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally

abnormal middle ear ossicle morphology ( J:132023 )

• mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium

• fragment is located where stapedius muscle is connected to temporal bone in wild-type ears

• no extra bone fragment associated with the malleus or incus was observed

• mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected ears

• bone bridges are not observed in unaffected or mildly affected ears

abnormal stapes morphology ( J:132023 )

• in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally

hearing/vestibular/ear

abnormal middle ear morphology ( J:132023 )

abnormal middle ear ossicle morphology ( J:132023 )

• mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium

• fragment is located where stapedius muscle is connected to temporal bone in wild-type ears

• no extra bone fragment associated with the malleus or incus was observed

• mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected ears

• bone bridges are not observed in unaffected or mildly affected ears

abnormal stapes morphology ( J:132023 )

• in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally

increased or absent threshold for auditory brainstem response ( J:132023 )

• Background Sensitivity: many animals on congenic background show increased ABR thresholds relative to wild-type mice; these animals hearing threshold shifts >10dB at 2 or more different frequencies in one or both ears

impaired hearing ( J:132023 )

• remaining mice do not show significant threshold differences from wild-type

conductive hearing loss ( J:132023 )

Genotype
MGI:3819381

ht13

• Allelic Composition: Nog^tm1Amc/Nog⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J * ICR

endocrine/exocrine glands

decreased prostate gland ventral lobe weight ( J:130204 )

♂ • at P35, ventral prostate lobe weight is significantly lower than in wild-type males

♂ • however, no differences in weights of dorsolateral prostate or coagulating gland weights or in numbers of main ducts, branch points or tips are observed relative to wild-type prostate lobes

reproductive system

decreased prostate gland ventral lobe weight ( J:130204 )

♂ • at P35, ventral prostate lobe weight is significantly lower than in wild-type males

♂ • however, no differences in weights of dorsolateral prostate or coagulating gland weights or in numbers of main ducts, branch points or tips are observed relative to wild-type prostate lobes

Genotype
MGI:3624838

ht14

• Allelic Composition: Nog^tm1Amc/Nog⁺
• Genetic Background: involves: 129S1/Sv * CD-1

skeleton

abnormal axial skeleton morphology ( J:108573 )

abnormal rib morphology ( J:108573 )

small thoracic cage ( J:108573 )

• reduced rib cage due to malformed ribs

kyphosis ( J:108573 )

• Background Sensitivity: in 30% of mice

fused synovial joints ( J:108573 )

• carpal and tarsal fusions in 100% of mice in all backgrounds

• no additional fusions throughout life

limbs/digits/tail

kinked tail ( J:108573 )

• in embryos at E14.5

Genotype
MGI:3819764

ht15

• Allelic Composition: Nog^tm1Amc/Nog⁺
• Genetic Background: involves: C57BL/6J * FVB

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:132023 )

N • Background Sensitivity: no hearing impairment is observed in heterozygous mice on a mixed background

Genotype
MGI:3819143

cx16

• Allelic Composition: Bmp7^tm1Kry/Bmp7^tm1Kry; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)

mortality/aging

prenatal lethality, complete penetrance ( J:118341 )

• no live mutants are recovered at birth

digestive/alimentary system

digestive/alimentary phenotype ( J:118341 )

N • foregut tubes show rescue of the narrowing defect seen in Nog-null embryos at E9.5

nervous system

nervous system phenotype ( J:118341 )

N • notochord development is largely rescued in double mutants in contrast to Nog-null embryos at E9.5; caudal neural tube is relatively normal at E11.5

Genotype
MGI:3034044

cx17

• Allelic Composition: Nbl1^tm1Rmh/Nbl1^tm1Rmh; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129S6/SvEvTac

skeleton

lumbar vertebral transformation ( J:67351 )

• vertebral transformation of the last lumbar vertebrae to a sacral fate

Genotype
MGI:3818001

cx18

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Nog^tm1Amc/Nog⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac

normal phenotype

no abnormal phenotype detected ( J:110617 )

• embryos show no abnormal phenotype

Genotype
MGI:3818000

cx19

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac

nervous system

nervous system phenotype ( J:110617 )

N • at E14, neural tube is closed, showing partial phenotypic rescue of neural tube defect seen in Nog-null embryos

skeleton

abnormal vertebrae development ( J:110617 )

• at E17, lumbar vertebrae are more developed than in Nog-null embryos

abnormal vertebral arch morphology ( J:110617 )

• neural arches are present but noticeably dysmorphic

Genotype
MGI:3723131

cx20

• Allelic Composition: Cer1^tm1Belo/Cer1^tm1Belo; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

prenatal lethality ( J:74136 )

• double homozygotes exhibit the same abnormalities as single homozygous Nog mutants

nervous system

abnormal neural tube closure ( J:74136 )

• abnormalities is neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon

open neural tube ( J:74136 )

exencephaly ( J:74136 )

• in mutants where the frontal, parietal and interparietal bones are absent, the brain is exposed at birth

skeleton

abnormal basicranium morphology ( J:74136 )

• fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology ( J:74136 )

• frontal bone is loose or absent

abnormal interparietal bone morphology ( J:74136 )

• interparietal bones are loose or absent

abnormal occipital bone morphology ( J:74136 )

• occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology ( J:74136 )

• parietal bone is loose or absent

limbs/digits/tail

short limbs ( J:74136 )

• truncated limbs

absent tail ( J:74136 )

craniofacial

abnormal basicranium morphology ( J:74136 )

• fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology ( J:74136 )

• frontal bone is loose or absent

abnormal interparietal bone morphology ( J:74136 )

• interparietal bones are loose or absent

abnormal occipital bone morphology ( J:74136 )

• occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology ( J:74136 )

• parietal bone is loose or absent

embryo

abnormal neural tube closure ( J:74136 )

• abnormalities is neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon

open neural tube ( J:74136 )

Genotype
MGI:2662585

cx21

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:60303 )

• no double homozygotes are recovered among neonates

• only 2 (out of 20 expected) double homozygotes are recovered close to term, both undergoing resorption

embryonic lethality during organogenesis, incomplete penetrance ( J:60303 )

• only 3 (out of 10 expected) double homozygotes are recovered at E12.5

embryonic lethality between somite formation and embryo turning, incomplete penetrance ( J:60303 )

• only 14 (out of 18 expected) double homozygotes are recovered at E8.5

nervous system

abnormal forebrain development ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive areas of the forebrain, anterior to the hindbrain

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

• anterior defects are noted at the start of neurulation (E7.5); however, the AVE is initially formed

• in contrast, formation of the midbrain and more posterior brain structures remains unaffected

aprosencephaly ( J:60303 )

• double homozygotes recovered at E12.5 display a more severe phenotype resembling aprosencephaly

holoprosencephaly ( J:60303 )

• double homozygotes recovered close to term exhibit holoprosencephaly

decreased forebrain size ( J:60303 )

• at E8.5, double homozygotes show significant loss of forebrain tissue

abnormal diencephalon morphology ( J:60303 )

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

abnormal telencephalon morphology ( J:60303 )

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

craniofacial

absent mandible ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit agnathia

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

abnormal facial morphology ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive facial structures

proboscis ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit a single nasal pit (proboscis)

skeleton

absent mandible ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit agnathia

absent sclerotome ( J:60303 )

• at E12.5, double homozygotes show absence of sclerotome in cervical regions

vision/eye

cyclopia ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit cyclopia

anophthalmia ( J:60303 )

• double homozygotes recovered at E12.5 lack eyes

taste/olfaction

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

respiratory system

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

tracheoesophageal fistula ( J:60303 )

• at E8.5, the trachea fails to form, and a common tracheo-esophageal duct connects the pharynx to the lungs and stomach

small pharynx ( J:60303 )

• at E8.5, the anterior pharynx is reduced

cardiovascular system

abnormal direction of heart looping ( J:60303 )

• at early somites stages, double homozygotes exhibit inverted cardiac looping, with the prospective heart ventricle looping to the left

embryo

abnormal mesendoderm development ( J:60303 )

• double homozygotes show defects in dorsal mesendoderm development (notochord, sclerotome, foregut)

abnormal left-right axis patterning ( J:60303 )

• at E8.5, 4 of 7 double homozygotes display heart inversions, indicating randomization of the heart situs

abnormal cephalic neural fold morphology ( J:60303 )

• at early somites stages, double homozygotes display a reduction in anterior neural folds

absent notochord ( J:60303 )

• at E12.5, double homozygotes show absence of a notochord in cervical regions

digestive/alimentary system

tracheoesophageal fistula ( J:60303 )

• at E8.5, the trachea fails to form, and a common tracheo-esophageal duct connects the pharynx to the lungs and stomach

growth/size/body

abnormal facial morphology ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive facial structures

proboscis ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit a single nasal pit (proboscis)

Genotype
MGI:2173453

cx22

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

cardiovascular system

abnormal direction of heart looping ( J:137629 )

• at E9.0 mutants show no directional looping of the heart; cardiac looping is abnormal or reversed in >90% of embryos

Genotype
MGI:4819102

cx23

• Allelic Composition: Nodal^tm1Rob/Nodal⁺; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

embryo

embryo phenotype ( J:161524 )

N • no defects are detected in anterior midline tissues

Genotype
MGI:4819098

cx24

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv

nervous system

holoprosencephaly ( J:161524 )

• in 29% of mice

embryo

abnormal mesendoderm development ( J:161524 )

• expression analysis indicates defects in patterning and function in the anterior most axial mesendoderm

abnormal embryonic tissue morphology ( J:161524 )

• 29% (17 of 58) show defects in anterior midline tissues

abnormal anterior definitive endoderm morphology ( J:161524 )

• expression analysis indicates impairment in ADE specification

abnormal prechordal plate morphology ( J:161524 )

• expression analysis indicates defects in patterning and function

abnormal primitive streak formation ( J:161524 )

• expression analysis indicates a defect in anterior primitive streak development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly		DOID:4621	OMIM:PS236100	J:161524

Genotype
MGI:4819101

cx25

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc; Smad3^tm1Xfw/Smad3^tm1Xfw
• Genetic Background: involves: 129/Sv * 129S1/Sv

nervous system

holoprosencephaly ( J:161524 )

• in 60% of mice

embryo

abnormal embryonic tissue morphology ( J:161524 )

• 60% (18 of 30) show defects in anterior midline tissues

Genotype
MGI:4819100

cx26

• Allelic Composition: Nog^tm1Amc/Nog⁺; Smad3^tm1Xfw/Smad3^tm1Xfw
• Genetic Background: involves: 129/Sv * 129S1/Sv

nervous system

holoprosencephaly ( J:161524 )

• in 2 of 16 mice

embryo

abnormal embryonic tissue morphology ( J:161524 )

• 13% (2 of 16) show defects in anterior midline tissues

Genotype
MGI:4819099

cx27

• Allelic Composition: Nog^tm1Amc/Nog⁺; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv

embryo

abnormal embryonic tissue morphology ( J:161524 )

• 5% (3 of 61) show defects in anterior midline tissues