Overview

Also Known As:Noggin KO

These Nog knock-out, lacZ reporter mice exhibit multiple defects, including an open neural tube, skeletal abnormalities, shortened body axis, and a small vestigial tail.

Donating Investigator

Andrew P McMahon, University of Southern California

Genetic overview

Genetic Background	Generation

Nog^tm1Amc

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Nog	noggin

View Genetics

Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Homozygous mice are born but die shortly after birth, exhibiting multiple defects, including an open neural tube, skeletal abnormalities, shortened body axis, and a small vestigial tail. Analysis of early gene expression has shown that the loss of Nog expression in the floorplate, notochord, and roofplate results in a progressive failure of ventral development in the CNS and somites. Nog is also expressed in condensing cartilage in the limb and in the sclerotome of somites so its loss results in defects in cartilage patterning and skeletal morphogenesis. Heterozygous embryos show lacZ reporter expression in pattern consistent with the endogenous gene.

Development

A targeting vector containing neomycin resistance, herpes simplex virus thymidine kinase and lacZ genes was used to disrupt most of the Nog coding region and some 3' flanking sequence. The targeted allele consists of an in frame lacZ fusion to noggin's first 10 amino acids. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to 129/Sv mice.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Expression of the lacZ reporter is consistent with the expression pattern of the endogenous gene.

Control Suggestions

Wild-type from the colony
002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

McMahon JA; Takada S; Zimmerman LB; Fan CM; Harland RM; McMahon AP. 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12(10):1438-52PubMed: 9585504 MGI: J:47724

View All References

Genetics

Nog^tm1Amc

Allele Symbol: Nog^tm1Amc

Allele Name	targeted mutation 1, Andrew P McMahon
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Nog^-; Nog^9E; noggin^-; Noggin^lacZ
Gene Symbol and Name	Nog, noggin
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Expression of the lacZ reporter is consistent with the expression pattern of the endogenous gene.
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	11
Molecular Note	Gene targeting generated a null allele by fusing the first 10 amino acids of coding sequence in-frame to the lacZ gene. The remainder of the coding sequence and some of the 3' flanking sequence of the gene were deleted. Ectopic expression of the resulting transcript was noted.
Mutations Made By	Andrew McMahon, University of Southern California

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

esophageal atresia/tracheoesophageal fistula

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Nog^tm1Amc related

Developmental Biology Research
- Postnatal Lethality
- Embryonic Lethality (Homozygous)
- Neural Tube Defects
- Neurodevelopmental Defects
- Skeletal Defects
Neurobiology Research
- Neural Tube Defects
- Neurodevelopmental Defects

Developmental Biology Research
- Perinatal Lethality
  - Homozygous
- Neurodevelopmental Defects
Research Tools
- lacZ Expression
- Developmental Biology Research
Neurobiology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: 129/Sv or (involves: 129S1/Sv * C57BL/6J)

embryo phenotype

abnormal neural tube morphology
- reduced in size

abnormal notochord morphology
- occasional side branching and buckling at E10.5

abnormal rostral-caudal patterning of the somites
- abnormalities become increasingly severe in a caudal direction

abnormal somite development

decreased embryo size

decreased somite size
- reduced

incomplete rostral neuropore closure
- Background Sensitivity - neural folds flatten at the 8-9 somite stage on the 129/Sv background
- 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 - on a mixed background the brain closes

growth/size/body region phenotype

decreased embryo size

hearing/vestibular/ear phenotype

abnormal ear development
- perturbed

integument phenotype

abnormal hair follicle development
- more apoptosis in hair placodes
- significantly reduced numbers of hair follicles and fewer reach an advanced stage of morphogenesis than normal

limbs/digits/tail phenotype

short limbs
- broad club shaped limbs

vestigial tail
- reduced at E12.5, absent later

mortality/aging

perinatal lethality, complete penetrance

nervous system phenotype

abnormal neural tube morphology
- reduced in size

abnormal spinal cord morphology
- becomes kinked on both backgrounds

incomplete rostral neuropore closure
- Background Sensitivity - neural folds flatten at the 8-9 somite stage on the 129/Sv background
- 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 - on a mixed background the brain closes

skeleton phenotype

abnormal axial skeleton morphology
- shortened axis between fore and hind limbs

vision/eye phenotype

abnormal eye development
- perturbed

Genotype: Nog^tm1Amc/Nog^tm1Amc
D1.129S1-Nog

mortality/aging

perinatal lethality

nervous system phenotype

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

Genotype: Nog^tm1Amc/Nog⁺
D1.129S1-Nog

craniofacial phenotype

abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears
- d ears
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears
- 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
- 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
- no extra bone fragment associated with the malleus or incus was observed

abnormal stapes morphology
- 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 styloid process morphology
- 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

limbs/digits/tail phenotype

kinked tail
- in embryos at E14.5

skeleton phenotype

abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears
- d ears
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears
- 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
- 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
- no extra bone fragment associated with the malleus or incus was observed

abnormal rib morphology

abnormal stapes morphology
- 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 styloid process morphology
- 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

fused synovial joints
- carpal and tarsal fusions in 100% of mice in all backgrounds
- no additional fusions throughout life

small thoracic cage
- reduced rib cage due to malformed ribs

hearing/vestibular/ear phenotype

abnormal middle ear morphology

abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears
- d ears
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears
- 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
- 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
- no extra bone fragment associated with the malleus or incus was observed

abnormal stapes morphology
- 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

conductive hearing loss

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

increased or absent threshold for auditory brainstem response
- 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

Genotype: Nog^tm1Amc/Nog^tm1Amc
B6.129S1-Nog

craniofacial phenotype

abnormal incus morphology
- at E17.5 incus is malformed

abnormal malleus morphology
- at E17.5 malleus is malformed

fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

skeleton phenotype

abnormal incus morphology
- at E17.5 incus is malformed

abnormal malleus morphology
- at E17.5 malleus is malformed

fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

embryo phenotype

small limb buds
- 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 phenotype

abnormal incus morphology
- at E17.5 incus is malformed

abnormal malleus morphology
- at E17.5 malleus is malformed

fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities

limbs/digits/tail phenotype

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance
- Background Sensitivity - embryo death before E14.5 on a B6.129S1 background

Genotype: Nog^tm1Amc/Nog⁺
B6.129S1-Nog

limbs/digits/tail phenotype

kinked tail
- in embryos at E14.5

skeleton phenotype

abnormal rib morphology

fused synovial joints
- carpal and tarsal fusions in 100% of mice in all backgrounds
- no additional fusions throughout life

small thoracic cage
- reduced rib cage due to malformed ribs

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * CD-1

cardiovascular system phenotype

hematoma
- 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

muscle phenotype

abnormal muscle fiber morphology
- myofibers in loose structures rather than tightly packed

abnormal muscle morphology
- reduced muscle tissue in newborns

nervous system phenotype

exencephaly
- Background Sensitivity - 60% penetrance, higher than on a DBA/1 background

skeleton phenotype

abnormal bone mineralization
- highly variable throughout the skeleton but characteristic for each region

fused synovial joints
- elbow fusion

embryo phenotype

abnormal limb bud morphology
- 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

growth/size/body region phenotype

decreased fetal size
- shorter along the rostral-caudal axis

homeostasis/metabolism phenotype

edema
- observed at E14.5

integument phenotype

abnormal hair follicle development
- rudimentary hair follicles at E18.5

limbs/digits/tail phenotype

abnormal limb bud morphology
- 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

abnormal limb morphology
- newbrons exhibit stubby limbs

vestigial tail
- degeneration of the tail structure is seen at E12.5

mortality/aging

perinatal lethality

Genotype: Nog^tm1Amc/Nog⁺
involves: 129S1/Sv * CD-1

limbs/digits/tail phenotype

kinked tail
- in embryos at E14.5

skeleton phenotype

abnormal axial skeleton morphology

abnormal rib morphology

fused synovial joints
- carpal and tarsal fusions in 100% of mice in all backgrounds
- no additional fusions throughout life

kyphosis
- Background Sensitivity - in 30% of mice

small thoracic cage
- reduced rib cage due to malformed ribs

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: C57BL/6

craniofacial phenotype

abnormal craniofacial morphology
- some mutants show severe craniofacial truncations

short face
- some mutants show mild facial truncations

embryo phenotype

abnormal neural tube morphology
- all homozygotes display spinal neural tube defects

growth/size/body region phenotype

short face
- some mutants show mild facial truncations

mortality/aging

perinatal lethality, complete penetrance
- mice all die perinatally

nervous system phenotype

abnormal neural tube morphology
- all homozygotes display spinal neural tube defects

exencephaly
- never observed on C57BL/6 inbred background

skeleton phenotype

abnormal skeleton morphology
- all homozygotes display severe skeletal malformations

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)

digestive/alimentary phenotype

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

esophagus stenosis
- severe narrowing of the esophagus is seen by E9.5

tracheoesophageal fistula
- 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 phenotype

abnormal neural tube morphology

incomplete rostral neuropore closure
- at E11.5 embryos show open brain phenotype

open neural tube
- at E11.5 caudal neural tube is open

respiratory system phenotype

tracheoesophageal fistula
- 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

embryo phenotype

abnormal neural tube morphology

abnormal notochord morphology
- abnormal at E8.5 and E9, indicating delayed detachment from dorsal foregut endoderm; appears hypertrophic compared to wild-type at E9
- 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
- no clear boundary between notochord and endoderm is detected at E8.5
- non-notochordal cells are observed within the notochord at E9.0

incomplete rostral neuropore closure
- at E11.5 embryos show open brain phenotype

open neural tube
- at E11.5 caudal neural tube is open

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

embryo phenotype

abnormal neural tube morphology
- severe neural tube defect is occasionally observed

growth/size/body region phenotype

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

nervous system phenotype

abnormal diencephalon morphology
- 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
- ventral diencephalon displays abnormalities

abnormal neural tube morphology
- severe neural tube defect is occasionally observed

abnormal pituitary gland development
- Rathke's pouch and anterior lobe development are severely affected
- 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)
- some cell specification appears to occur in pituitary tissue

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

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

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

absent pituitary gland
- 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

absent pituitary infundibular stalk
- morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5

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

endocrine/exocrine gland phenotype

abnormal pituitary gland development
- Rathke's pouch and anterior lobe development are severely affected
- 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)
- some cell specification appears to occur in pituitary tissue

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

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

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

absent pituitary gland
- 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

absent pituitary infundibular stalk
- morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5

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

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * C57BL/6J * ICR

digestive/alimentary phenotype

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

limbs/digits/tail phenotype

absent tail
- some embryos exhibit agenesis of the tail

renal/urinary system phenotype

abnormal urethra morphology
- angle between bladder neck and urethra in urogenital sinus (UGS) is much larger than the approximate 90 degrees seen in wild-type embryos
- some males exhibit agenesis of the membranous (pelvic) urethra while others develop a preursor urethral epithelial tube

abnormal urinary system development

pelvic kidney
- occasionally an ectopic kidney is observed in the pelvic cavity

reproductive system phenotype

abnormal male reproductive system morphology
- dorsal ridges are absent or reduced in size; dorsal sulcus is missing and ejaculatory duct connection is exposed

abnormal prostate gland development
- in developing embryos the ventral prostate (VP) bud is absent
- in developing prostate the coagulating gland bud is absent

abnormal prostate gland morphology
- dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos

absent bulbourethral gland
- some males show agenesis of the bulbourethral gland

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

embryo phenotype

abnormal primitive urogenital sinus morphology
- UGS is smaller at E17 in males

abnormal septation of the cloaca
- 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 E17 males have a fistulous connection between hindgut and dorsal surface of UGS; females show similar defects at E17
- at P1 this is observed as reduction in ventral mesenchyme pad thickness and density
- incomplete separation of the hindgut from the urogenital sinus (UGS) is observed in some embryos
- UGS

endocrine/exocrine gland phenotype

abnormal prostate gland development
- in developing embryos the ventral prostate (VP) bud is absent
- in developing prostate the coagulating gland bud is absent

abnormal prostate gland morphology
- dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos

absent bulbourethral gland
- some males show agenesis of the bulbourethral gland

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

Genotype: Nog^tm1Amc/Nog⁺
involves: 129S1/Sv * C57BL/6J * ICR

endocrine/exocrine gland phenotype

small prostate gland ventral lobe
- at P35 ventral prostate lobe weight is significantly lower than in wild-type males
- Normal - 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 phenotype

small prostate gland ventral lobe
- at P35 ventral prostate lobe weight is significantly lower than in wild-type males
- Normal - 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: Nog^tm1Amc/Nog⁺
involves: C57BL/6J * FVB

mammalian phenotype

hearing/vestibular/ear phenotype
- Background Sensitivity - no hearing impairment is observed in heterozygous mice on a mixed background

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * C57BL/6J * FVB/N

hearing/vestibular/ear phenotype

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

decreased cochlear coiling
- cochleae of controls show 1.75 turns compared to only 1 turn in mutants

increased cochlear inner hair cell number
- 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
- 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

nervous system phenotype

increased cochlear inner hair cell number
- 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
- 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

The following phenotype relates to a compound genotype created using this strain

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv

cellular phenotype

increased apoptosis

craniofacial phenotype

abnormal basicranium morphology
- fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology
- frontal bone is loose or absent

abnormal interparietal bone morphology
- interparietal bone is loose or absent

abnormal occipital bone morphology
- occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology
- parietal bone is loose or absent

limbs/digits/tail phenotype

absent tail

short limbs
- truncated limbs

mortality/aging

perinatal lethality, complete penetrance
- mice all die perinatally
- time of death not specified

nervous system phenotype

abnormal neural plate morphology
- neural plate shows furrows and kinks in open cranial portion and closed spinal portion

abnormal neural tube closure
- abnormalities in neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon
- walls of neural tube remain relatively flat or convex rather than bending to form concave walls

abnormal neural tube morphology
- all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs)
- at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured
- between the limbs, flattened neural mass beneath edematous tissue replaces neural tube
- defective neurulation is detected at E9.0
- neural tube at level of forelimbs is mildly affected

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

exencephaly
- 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
- in mutants where the frontal, parietal and interparietal bones are absent, the brain is exposed at birth
- large convoluted mass of brain tissue protrudes from head
- midbrain and hindbrain regions are directly exposed to extraembryonic environment

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

kinked neural tube
- observed in embryos at E8 or E9

open neural tube

spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

wavy neural tube
- observed in embryos at E8 or E9

respiratory system phenotype

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

abnormal lung morphology
- at E15.5 all mice have abnormal lungs with malformed and truncated lobes

abnormal right lung morphology
- fusions of the right lobes are seen in 78% of embryos

skeleton phenotype

abnormal axial skeleton morphology
- 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
- fusion of presphenoid, basisphenoid, and basioccipital bones

abnormal frontal bone morphology
- frontal bone is loose or absent

abnormal interparietal bone morphology
- interparietal bone is loose or absent

abnormal occipital bone morphology
- occipital condyles are loose, showing variability in the distance separating them

abnormal parietal bone morphology
- parietal bone is loose or absent

abnormal vertebral arch morphology
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

absent vertebral arch
- caudal to forelimb, dorsal neural arches are absent

spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

embryo phenotype

abnormal neural plate morphology
- neural plate shows furrows and kinks in open cranial portion and closed spinal portion

abnormal neural tube closure
- abnormalities in neural tube closure, particularly in the brain vesicles between the diencephalons and myelencephalon
- walls of neural tube remain relatively flat or convex rather than bending to form concave walls

abnormal neural tube morphology
- all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs)
- at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured
- between the limbs, flattened neural mass beneath edematous tissue replaces neural tube
- defective neurulation is detected at E9.0
- neural tube at level of forelimbs is mildly affected

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

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

kinked neural tube
- observed in embryos at E8 or E9

open neural tube

spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact

wavy neural tube
- observed in embryos at E8 or E9

References

McMahon JA; Takada S; Zimmerman LB; Fan CM; Harland RM; McMahon AP. 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12(10):1438-52PubMed: 9585504 MGI: J:47724

Additional References

Brunet LJ; McMahon JA; McMahon AP; Harland RM. 1998. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton [see comments] Science 280(5368):1455-7PubMed: 9603738 MGI: J:48000

Additional - Nog^tm1Amc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Nog
- Genotyping resources and troubleshooting
Breeding Considerations

The strain originated on and is currently on a 129/Sv background. Homozygotes are not viable. The investigator maintains the strain by breeding heterozygotes or heterozygous males with 129/SvJ females.
- Additional Breeding and Husbandry Support
Citation
When using the Noggin KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003383 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Nog<tm1Amc>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:Noggin KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Nogtm1Amc

Allele Symbol: Nogtm1Amc

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Nogtm1Amc related

Mammalian Phenotype Terms by Genotype

Genotype: Nogtm1Amc/Nogtm1Amceither: 129/Sv or (involves: 129S1/Sv * C57BL/6J)

embryo phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

integument phenotype

limbs/digits/tail phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

vision/eye phenotype

Genotype: Nogtm1Amc/Nogtm1AmcD1.129S1-Nog

mortality/aging

nervous system phenotype

Genotype: Nogtm1Amc/Nog+D1.129S1-Nog

craniofacial phenotype

limbs/digits/tail phenotype

skeleton phenotype

hearing/vestibular/ear phenotype

Genotype: Nogtm1Amc/Nogtm1AmcB6.129S1-Nog

craniofacial phenotype

skeleton phenotype

embryo phenotype

hearing/vestibular/ear phenotype

limbs/digits/tail phenotype

mortality/aging

Genotype: Nogtm1Amc/Nog+B6.129S1-Nog

limbs/digits/tail phenotype

skeleton phenotype

Genotype: Nogtm1Amc/Nogtm1Amcinvolves: 129S1/Sv * CD-1

cardiovascular system phenotype

muscle phenotype

nervous system phenotype

skeleton phenotype

embryo phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

integument phenotype

limbs/digits/tail phenotype

mortality/aging

Genotype: Nogtm1Amc/Nog+involves: 129S1/Sv * CD-1

limbs/digits/tail phenotype

skeleton phenotype

Genotype: Nogtm1Amc/Nogtm1Amcinvolves: C57BL/6

craniofacial phenotype

embryo phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

Genotype: Nogtm1Amc/Nogtm1Amceither: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)

digestive/alimentary phenotype

nervous system phenotype

respiratory system phenotype

embryo phenotype

Genotype: Nogtm1Amc/Nogtm1Amceither: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

embryo phenotype

growth/size/body region phenotype

nervous system phenotype

endocrine/exocrine gland phenotype

Genotype: Nogtm1Amc/Nogtm1Amcinvolves: 129S1/Sv * C57BL/6J * ICR

digestive/alimentary phenotype

Nog^tm1Amc

Allele Symbol: Nog^tm1Amc

Genotype: Nog^tm1Amc related

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: 129/Sv or (involves: 129S1/Sv * C57BL/6J)

Genotype: Nog^tm1Amc/Nog^tm1Amc
D1.129S1-Nog

Genotype: Nog^tm1Amc/Nog⁺
D1.129S1-Nog

Genotype: Nog^tm1Amc/Nog^tm1Amc
B6.129S1-Nog

Genotype: Nog^tm1Amc/Nog⁺
B6.129S1-Nog

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * CD-1

Genotype: Nog^tm1Amc/Nog⁺
involves: 129S1/Sv * CD-1

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: C57BL/6

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)

Genotype: Nog^tm1Amc/Nog^tm1Amc
either: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * C57BL/6J * ICR

Genotype: Nog^tm1Amc/Nog⁺
involves: 129S1/Sv * C57BL/6J * ICR

Genotype: Nog^tm1Amc/Nog⁺
involves: C57BL/6J * FVB

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv * C57BL/6J * FVB/N

Genotype: Nog^tm1Amc/Nog^tm1Amc
involves: 129S1/Sv

Additional - Nog^tm1Amc related