Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?pN1 Generation Definitions   Donating Investigator Todd Camenisch,   University of Arizona

Description
While heterozygous mice are viable and fertile, mice homozygous for this targeted allele die between embryonic day (E)9.5 and E10.5. Embryonic mRNA expression from the targeted gene shows only truncated transcripts of the expected length, with no full-length mRNA expression. Homozygous embryos exhibit severe cardiac and vascular abnormalities, lack hyaluronan (HA), and have yolk sac and somite deformities. Heart deformities can be rescued in explants from homozygous mice following exogenous HA or activated H-Ras treatment. These Has2 mutant mice may be useful in studying embryogenesis and development, specifically cardiac and vascular morphogenesis, as well as cell transformation.

Development
A targeting vector was designed to replace a portion of intron 3 (including the splice acceptor) and the first 60 codons of exon 4 (encoding part of the cytoplasmic catalytic domain) of the targeted gene with a PGK-Neo cassette in reverse orientation. The construct was electroporated into 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6J blastocysts, and chimeric offspring were bred to C57BL/6J mice. Heterozygous mutants were maintained on this mixed genetic background for many generations prior to arrival at The Jackson Laboratory. Upon arrival, these mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	100492 B6129PF1/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Has2^tm1Jam/Has2^tm1Jam

        involves: 129P2/OlaHsd * C57BL/6J

• mortality/aging
• complete embryonic lethality during organogenesis
  • homozygotes die during midgestation between E.9.5 and E10   (MGI Ref ID J:63748)
  • partial resorptions are first observed at E11.5   (MGI Ref ID J:63748)
• cardiovascular system phenotype
• abnormal blood vessel morphology
  • at E9.5, homozygotes show absence of an organized vascular network relative to wild-type   (MGI Ref ID J:63748)
• • absent vitelline blood vessels
    • mutant embryos contain scant numbers of red blood cells and lack vessels in the yolk sac   (MGI Ref ID J:63748)
• abnormal cardiac epithelial to mesenchymal transition
  • in an explant system, homozygotes show absent cell migration and epithelium-to-mesenchyme transformation in the atrioventricular (AV) canal and outflow tract; transformation is rescued by Has2 cDNA or the addition of purified HA   (MGI Ref ID J:63748)
• abnormal heart morphology
  • mutant hearts show significant compaction of the extracellular space   (MGI Ref ID J:63748)
  • homozygotes lack alcian blue-staining glycosaminoglycans and HA in cardiac jelly; in contrast, collagen I, fibronectin, laminin, and versican are present   (MGI Ref ID J:63748)
• • abnormal cardiac jelly morphology
    • mutant hearts display absence of cardiac jelly   (MGI Ref ID J:63748)
  • absent atrioventricular cushions
    • mutant hearts display absence of cardiac jelly and cushions, despite a characteristic constriction at the atrioventricular (AV) region   (MGI Ref ID J:63748)
  • absent trabeculae carneae
    • the mutant myocardium lacks trabeculae even though the ventricular wall is several cell layers thick   (MGI Ref ID J:63748)
  • atrium hypoplasia
    • at E9.5, the mutant atrium is smaller than wild-type   (MGI Ref ID J:63748)
  • decreased heart right ventricle size
    • at E9.5, homozygotes dispaly a significant reduction of the right ventricle   (MGI Ref ID J:63748)
  • pericardial edema
    • mutant hearts often display significant pericardial swelling   (MGI Ref ID J:63748)
• abnormal outflow tract development
  • mutant hearts show partial or complete obstruction of the outflow tract   (MGI Ref ID J:63748)
• irregular heartbeat
  • hearts of viable homozygotes beat with a distinctive to-and-fro motion of red blood cells   (MGI Ref ID J:63748)
• embryogenesis phenotype
• abnormal embryonic tissue morphology
  • at E9.5, homozygotes show posterior defects   (MGI Ref ID J:63748)
• • abnormal mesenchyme morphology
    • at E9.5, homozygotes show cephalic mesenchyme abnormalities   (MGI Ref ID J:63748)
  • abnormal somite shape
    • at E9.5, somites are present but appear distorted; other structures including the first pharyngeal pouch and otic placodes are also present   (MGI Ref ID J:63748)
• abnormal extraembryonic endoderm formation
  • in homozygotes, the visceral endoderm and mesoderm that form the yolk sac fail to fuse except at discrete foci; red blood cells are free within this space   (MGI Ref ID J:63748)
• abnormal visceral yolk sac morphology
  • mutant yolk sacs have a punctate appearance   (MGI Ref ID J:63748)
• absent vitelline blood vessels
  • mutant embryos contain scant numbers of red blood cells and lack vessels in the yolk sac   (MGI Ref ID J:63748)
• embryonic growth retardation
  • occasionally, viable embryos are detected at E10.5 with beating hearts and significant growth retardation   (MGI Ref ID J:63748)
• incomplete embryo turning
  • at E9.5, some homozygous mutant embryos have failed to turn   (MGI Ref ID J:63748)
• growth/size phenotype
• embryonic growth retardation
  • occasionally, viable embryos are detected at E10.5 with beating hearts and significant growth retardation   (MGI Ref ID J:63748)
• homeostasis/metabolism phenotype
• pericardial edema
  • mutant hearts often display significant pericardial swelling   (MGI Ref ID J:63748)
• muscle phenotype
• absent trabeculae carneae
  • the mutant myocardium lacks trabeculae even though the ventricular wall is several cell layers thick   (MGI Ref ID J:63748)

View Research Applications

Research Applications

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

Cancer Research
Defects in Cell Adhesion Molecules
Other

Cardiovascular Research
Heart Abnormalities
Other
Vascular Defects

Cell Biology Research
Defects in Extracellular Matrix Molecules

Developmental Biology Research
Defects in Extracellular Matrix Molecules
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      heart
      heart: vasculature

Internal/Organ Research
Heart Abnormalities

Research Tools
Cancer Research
Cardiovascular Research
Developmental Biology Research
Internal/Organ Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Has2tm1Jam
Allele Name		targeted mutation 1, John A McDonald
Allele Type		Targeted (knock-out)
Common Name(s)		Has2-;
Mutation Made By		Todd Camenisch,   University of Arizona
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		GK129
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Has2, hyaluronan synthase 2
Chromosome		15
Molecular Note		The gene was disrupted by replacement of the end of intron 3 and the first 60 codons of the cytoplasmic catalytic domain containing exon 4 with a PGK-neo cassette via homologous recombination. Homozygous mutant embryos were observed at days E9.5-E11.5 and RT-PCR analysis of embryonic mRNA detected truncated mutant transcripts. [MGI Ref ID J:63748]

Genotyping

Genotyping Information

Genotyping Protocols

Has2^tm1Jam, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Camenisch TD; Spicer AP; Brehm-Gibson T; Biesterfeldt J; Augustine ML; Calabro A Jr; Kubalak S; Klewer SE; McDonald JA. 2000. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme [see comments] J Clin Invest 106(3):349-60. [PubMed: 10930438]  [MGI Ref ID J:63748]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred together, or to wildtype siblings. Homozygous mice die in utero.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	100492 B6129PF1/J	(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

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.