Description

Strain Information

Former Names 129S1.C3H(B6)-Grhl21Nisw/J    (Changed: 29-MAR-11 ) Type Chemically Induced Mutation; Congenic; Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Wild-type x Heterozygote         (Female x Male)   20-AUG-12 Mating System Heterozygote x Wild-type         (Female x Male)   20-AUG-12 Species laboratory mouse Generation N9pN1+F1 (11-DEC-12) Generation Definitions   Donating Investigator Lee Niswander,   University of Colorado, Denver

Description
Mice homozygous for the ENU-induced mutation, Grhl2^1Nisw, die by E10.5. Heterozygotes are viable and fertile. The nonsense mutation in the grainyhead-like 2 (Grhl2) gene, results in a premature stop codon. Homozygotes exhibit complete exencephaly (hind-mid-forebrain) and cleft face, wherein the upper jaw and upper part of the face fail to close, but the lower jaw is formed. They also have heart and lung defects and low penetrance syndactyly. Expression of this mutation is found in the non-neural/epidermal ectoderm from E8.5 to E10.5. These mutant mice may be useful in studying embryonic development.

Development
Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify mice (Line2F) exhibiting defects in the closure of embryonic fissures (including the neural tube, body wall, and face). Using a candidate gene approach a mutation was identified on Chromosome 15. Using genomic sequence capture and high throughput sequencing, a single nucleotide polymorphism (SNP), SNP178, encoding a premature stop codon, was found in the grainyhead-like 2 (Grhl2) gene. These Grhl2^1Nisw mice were bred to littermates and then to C3H3B/FeJ mice. Subsequently, these mice were backcrossed to 129S1/SvImJ for at least 9 generations to maintain a colony. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Deafness, Autosomal Dominant 28; DFNA28   (GRHL2)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Grhl2^m1Nisw/Grhl2^m1Nisw

        129S1.B6-Grhl2^m1Nisw

• mortality/aging
• partial embryonic lethality during organogenesis
  • most mice die at E9.5   (MGI Ref ID J:169829)
• partial lethality
  • most mice die at E9.5   (MGI Ref ID J:169829)
• reproductive system phenotype
• decreased litter size
  • female mice yield smaller than expected litters compared with wild-type mice   (MGI Ref ID J:169829)
• cardiovascular system phenotype
• abnormal heart morphology
  • anemic heart at E18.5   (MGI Ref ID J:169829)
• • abnormal heart ventricle morphology
    • at E18.5, ventricles contain larger spaces than in wild-type mice   (MGI Ref ID J:169829)
  • • thin ventricular wall
      • at E14.5   (MGI Ref ID J:169829)
• embryogenesis phenotype
• decreased embryo size
  • at E10.5   (MGI Ref ID J:169829)
• embryonic growth retardation
  • at E10.5   (MGI Ref ID J:169829)
• open neural tube
  • at E10.5, mice exhibit open, wavy neural folds unlike in wild-type mice   (MGI Ref ID J:169829)
  • however, mice exhibit normal patterning, proliferation, and differentiation in the neural tube   (MGI Ref ID J:169829)
• growth/size phenotype
• decreased embryo size
  • at E10.5   (MGI Ref ID J:169829)
• embryonic growth retardation
  • at E10.5   (MGI Ref ID J:169829)
• herniated abdominal wall
  • primary thoracoabdominoschisis in all mice at E12.5 or later   (MGI Ref ID J:169829)
• thoracoschisis
  • primary thoracoabdominoschisis in all mice at E12.5 or later   (MGI Ref ID J:169829)
• nervous system phenotype
• exencephaly
  • in the hind-, mid-, and forebrain   (MGI Ref ID J:169829)
• open neural tube
  • at E10.5, mice exhibit open, wavy neural folds unlike in wild-type mice   (MGI Ref ID J:169829)
  • however, mice exhibit normal patterning, proliferation, and differentiation in the neural tube   (MGI Ref ID J:169829)
• respiratory system phenotype
• abnormal respiratory conducting tube morphology
  • small and collapsed at E18.5   (MGI Ref ID J:169829)
• small lung lobe   (MGI Ref ID J:169829)
• craniofacial phenotype
• facial cleft
  • with upper jaw and upper part of the face failing to close   (MGI Ref ID J:169829)
  • however, the lower jaw is normal   (MGI Ref ID J:169829)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Grhl2^m1Nisw/Grhl2^m1Nisw

        involves: C3HeB/FeJ * C57BL/6J

• mortality/aging
• complete lethality throughout fetal growth and development
  • some mice survive to E18.5 on a mixed background some mice survive to E18.5   (MGI Ref ID J:169829)
• partial lethality
  • some mice survive to E18.5   (MGI Ref ID J:169829)
• craniofacial phenotype
• abnormal cranium morphology
  • at E18.5, mice lack components of the top of the skull and midface unlike wild-type mice   (MGI Ref ID J:169829)
  • however, mice exhibit normal lower jaw and ventral skull   (MGI Ref ID J:169829)
• abnormal facial morphology
  • at E18.5, mice lack components of the midface unlike wild-type mice   (MGI Ref ID J:169829)
• • facial cleft
    • all mice exhibit cleft face or unilateral or bilateral cleft   (MGI Ref ID J:169829)
• skeleton phenotype
• abnormal cranium morphology
  • at E18.5, mice lack components of the top of the skull and midface unlike wild-type mice   (MGI Ref ID J:169829)
  • however, mice exhibit normal lower jaw and ventral skull   (MGI Ref ID J:169829)
• split sternum   (MGI Ref ID J:169829)
• limbs/digits/tail phenotype
• syndactyly
  • of soft tissue   (MGI Ref ID J:169829)
• • interdigital webbing
    • in some mice   (MGI Ref ID J:169829)
• nervous system phenotype
• exencephaly
  • in all mice   (MGI Ref ID J:169829)
• open neural tube
  • at E9.5   (MGI Ref ID J:169829)
  • however, neural folds elevate normally   (MGI Ref ID J:169829)
• embryogenesis phenotype
• open neural tube
  • at E9.5   (MGI Ref ID J:169829)
  • however, neural folds elevate normally   (MGI Ref ID J:169829)
• growth/size phenotype
• abnormal body wall morphology
  • in 50% of mice   (MGI Ref ID J:169829)
• vision/eye phenotype
• coloboma   (MGI Ref ID J:169829)

View Research Applications

Research Applications

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

Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      heart
      lung
Neural Tube Defects
Skeletal Defects
      syndactyly

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Grhl2m1Nisw
Allele Name		mutation 1, Lee Niswander
Allele Type		Chemically induced (ENU)
Common Name(s)		Grhl21Nisw;
Mutation Made By		Lee Niswander,   University of Colorado, Denver
Strain of Origin		C57BL/6J
Gene Symbol and Name		Grhl2, grainyhead-like 2 (Drosophila)
Chromosome		15
Gene Common Name(s)		0610015A08Rik; BOM; DFNA28; RGD1561191; RIKEN cDNA 0610015A08 gene; TFCP2L3; Tcfcp2l3; transcription factor CP2-like 3;
Molecular Note		ENU induced a T to A transversion at position 37,200,529 on chromosome 15 that results in the production of a premature stop codon. The predicted product contains 52 amino acids compared with the full length 625 amino acids. [MGI Ref ID J:169829]

Genotyping

Genotyping Information

Genotyping Protocols

Grhl2^1Nisw, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pyrgaki C; Liu A; Niswander L. 2011. Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion. Dev Biol :. [PubMed: 21377456]  [MGI Ref ID J:169829]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred to wildtype from the colony or to 129S1/SvImJ mice(Stock No. 002448). Homozygous mice die by E10.5.
Mating System	Wild-type x Heterozygote         (Female x Male)   20-AUG-12
	Heterozygote x Wild-type         (Female x Male)   20-AUG-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.