Overview

Also Known As:forebrain overgrowth

These mice carry a spontaneous mutation at the Apaf1 locus characterized by forebrain, lumbo-sacral, and facial defects.

Genetic overview

Genetic Background	Generation

Apaf1^fog

Allele Type	Gene Symbol	Gene Name
Spontaneous (Hypomorph)	Apaf1	apoptotic peptidase activating factor 1

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Research Applications

Neurobiology Research
Reproductive Biology Research
Cell Biology Research
Apoptosis Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the forebrain overgrowth recessive spontaneous mutation (fog) display forebrain, lumbo-sacral, and facial defects most likely due to excessive growth or cellular proliferation ultimately causing abnormalities in neural tube closure. The phenotypes manifest as head bumps and sacral spina bifida and individual mice can have either or both. Three unique features of the mutant are (1) the growth of telencephalon cells into the surrounding mesenchyme, (2) presence of an encephalocele through the midline cleft in some mutants, and (3) dissociation of the tail defect from the caudal neural tube defect. The fog mutation maps to mouse Chromosome 10 near D10Mit262 and D10Mit230.

Control Suggestions

Heterozygote from the colony
Untyped from the colony
+/? sibling

Additional Information

Considerations for Choosing Controls

Genetics

Apaf1^fog

Allele Symbol: Apaf1^fog

Allele Name	forebrain overgrowth
Allele Type	Spontaneous (Hypomorph)
Allele Synonym(s)	Apaf-1^fog; fog
Gene Symbol and Name	Apaf1, apoptotic peptidase activating factor 1
Gene Synonym(s)
Strain of Origin	STOCK Ggt1^dwg/J
Chromosome	10
General Note	Mutant mice are characterized by forebrain overgrowth and excessive cellular proliferation in the midline cleft. Human APAF1 is a candidate gene for Noonan Syndrome (OMIM 163950), a complex disease with some patients showing facial, cardiac, retinal, and limb abnormalities reminiscent of defective apoptosis (J:49840).
Molecular Note	Defective mRNA processing appears to be the cause of the markedly reduced normal mRNA levels, protein levels, and activity in fog mutant mice. Complementation testing confirmed that the fog mutant mouse is an allele of Apaf1.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Apaf1^fog related

Neurobiology Research
- Neurodevelopmental Defects
- Neural Tube Defects
Reproductive Biology Research
- Fertility Defects
Cell Biology Research
- Signal Transduction
Apoptosis Research
Developmental Biology Research
- Neural Tube Defects
- 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: Apaf1^fog/Apaf1^fog
involves: C3H/HeJ

embryo phenotype

spina bifida occulta
- spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)
- lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
- persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals

abnormal embryonic neuroepithelium morphology
- some cell death is observed in lesions of telencephalic walls at E10.5
- cells are less densely packed and protrude slightly into lumen of lateral ventricle

spina bifida
- animals also display mild-to-moderate lumbar spina bifida

delayed neural tube closure
- at E10.5, cranial neuropore is still open whereas it is closed in wild-type embryos; closure in essentially all mutants is observed at E12.5

growth/size/body region phenotype

abnormal forehead shape
- affected animals exhibit usually bilateral bumps over the forehead; bumps may be larger on one side or give the appearance of a wholly enlarged forehead
- in adult mice, bumps usually contain loose connective tissue

midline facial cleft
- a few embryos exhibit facial clefting at E12 and later; mutant embryos observed at E16.5-17.5 display herniation of entire forebrain through middle of face

short snout
- affected animals may show shorter snouts

cardiovascular system phenotype

intracerebral hemorrhage
- in some foci of proliferation, rupture of blood vessels occurs, causing hemorrhages into parenchyma of cerebral hemispheres
- by E17.5, massive hemorrhage in brain and subectodermal tissue of the frontal bulges can be seen through the skin

limbs/digits/tail phenotype

kinked tail
- tails are malformed in about half of the mutants; tails may show distal kinks

curly tail
- around 50% of mutants may display curly or looped tails, shaped like a corkscrew; may be present singly (20%) or in combination with exencephaly and/or spina bifida (40%)

mammalian phenotype

nervous system phenotype
- Normal - in adult animals, neuronal counts of spinal and cranial motoneurons, spinal interneurons, dorsal root ganglion sensory neurons, and superior cervical ganglion sympathetic neurons are not different from wild-type

mortality/aging

perinatal lethality, incomplete penetrance
- severity of defects results in death at or shortly after birth

postnatal lethality, incomplete penetrance
- severity of defects results in death shortly after birth; preweaning lethality is 6%

decreased survivor rate
- some mice, including animals with combinations of most or all defects do survive to adulthood and reproduce

nervous system phenotype

abnormal forebrain morphology
- in embryos (E17.5), herniation of forebrain tissue may be observed; forebrain is enlarged
- at E13.5-14.5, mass of forebrain tissue has increased due to hemorrhage and multifocal proliferation such that cerebral hemispheres are starting to bulge from surface of head; by E17.5, forebrain tissue mass compressed overlying subepidermal mesenchyme

abnormal telencephalon morphology
- at E10.5, telencephalic walls are folded in embryos with open cranial neuropore
- lesions of telencephalic walls are detected at E10.5
- cells of walls extrude outwardly, compressing connective tissue of meninges and subepidermal mesenchyme which will form calvaria; such extrusions are observed extending into mesenchyme around basal forebrain and sometimes penetrate wall of the pharynx

exencephaly
- in adult homozygotes, exencephalic forebrain is covered by skin and hair an appears as forehead bumps
- mutants show exencephaly or herniation of the forebrain; may be present singly or in combination with tail defects and/or spina bifida
- forebrain exencephaly is observed, similar to other Apaf1-null mutants

intracerebral hemorrhage
- by E17.5, massive hemorrhage in brain and subectodermal tissue of the frontal bulges can be seen through the skin
- in some foci of proliferation, rupture of blood vessels occurs, causing hemorrhages into parenchyma of cerebral hemispheres

abnormal lateral ventricle morphology
- lumen of ventricles are narrower than wild-type at E12.5; ventricles often contain blood
- at E10.5, embryos with open cranial neuropore display collapsed lateral ventricles
- cells of telencephalic walls are less densely packed than in wild-type and protrude slightly into lumen of lateral ventricle at E10.5; at E12.5, protrusions are more conspicuous with more cells and vascularization

abnormal embryonic neuroepithelium morphology
- some cell death is observed in lesions of telencephalic walls at E10.5
- cells are less densely packed and protrude slightly into lumen of lateral ventricle

abnormal cerebral hemisphere morphology
- at E13.5 and E14.5, cerebral hemispheres show many folds and intraparenchymal proliferation foci
- mesenchymal and epidermal cover of hemispheres is extremely thin on top

delayed neural tube closure
- at E10.5, cranial neuropore is still open whereas it is closed in wild-type embryos; closure in essentially all mutants is observed at E12.5

abnormal cranial flexure morphology
- absence of cephalic flexure in rostrally extended brain

spina bifida
- animals also display mild-to-moderate lumbar spina bifida

spina bifida occulta
- lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
- persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals
- spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)

reproductive system phenotype

reduced female fertility
- some adult females breed poorly or do not reproduce

reduced male fertility
- some adult males breed poorly or do not reproduce

skeleton phenotype

spina bifida occulta
- lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
- persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals
- spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)

abnormal cranium morphology
- in mutant embryos with facial clefts observed at E16.5-17.5, skulls are flat due to absence of cephalic flexure in rostrally extended brain

abnormal neurocranium morphology
- show normal sutures, but one to three round holes up to 3 mm in diameter) mark sites where ossification had been impaired by enlarged forebrain

craniofacial phenotype

abnormal neurocranium morphology
- show normal sutures, but one to three round holes up to 3 mm in diameter) mark sites where ossification had been impaired by enlarged forebrain

short snout
- affected animals may show shorter snouts

abnormal forehead shape
- in adult mice, bumps usually contain loose connective tissue
- affected animals exhibit usually bilateral bumps over the forehead; bumps may be larger on one side or give the appearance of a wholly enlarged forehead

abnormal cranium morphology
- in mutant embryos with facial clefts observed at E16.5-17.5, skulls are flat due to absence of cephalic flexure in rostrally extended brain

midline facial cleft
- a few embryos exhibit facial clefting at E12 and later; mutant embryos observed at E16.5-17.5 display herniation of entire forebrain through middle of face

References

Additional References

Harris BS; Franz T; Ullrich S; Cook S; Bronson RT; Davisson MT. 1997. Forebrain overgrowth (fog): a new mutation in the mouse affecting neural tube development. Teratology 55(4):231-40PubMed: 9216040 MGI: J:41353

Additional - Apaf1^fog related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together or to wildtype mice from the colony. Heterozygous mice breed fine, but breeding heterozygous x heterozygous produces less than the expected 25% homozygotes in the offspring. In 1999, the donating investigator's lab reported that the few homozygotes which survive to adulthood are usually poor breeders - even though male meiosis appears normal at the light microscope level.
- Additional Breeding and Husbandry Support
Appearance
- agouti
  Related Genotype: A/A
Citation
When using the forebrain overgrowth mouse strain in a publication, please cite the originating article(s) and include JAX stock #002979 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
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Homozygous for Apaf1<fog>, 1 pair minimum

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.

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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:forebrain overgrowth

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Apaf1fog

Allele Symbol: Apaf1fog

Disease Terms

Research Areas By Phenotype

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

Genotype: Apaf1fog related

Mammalian Phenotype Terms by Genotype

Genotype: Apaf1fog/Apaf1foginvolves: C3H/HeJ

embryo phenotype

growth/size/body region phenotype

cardiovascular system phenotype

limbs/digits/tail phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

reproductive system phenotype

skeleton phenotype

craniofacial phenotype

References

Additional References

Additional - Apaf1fog related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Apaf1^fog

Allele Symbol: Apaf1^fog

Genotype: Apaf1^fog related

Genotype: Apaf1^fog/Apaf1^fog
involves: C3H/HeJ

Additional - Apaf1^fog related