Description

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote         (Female x Male) Species laboratory mouse   Donating Investigator Donna King,   N East Ohio Univ Coll of Med (NEOUCOM)

Description
Mice hemizygous for this transgene are viable. While males are fertile, transgenic females are unreliable breeders and mothers. Homozygotes are sterile. In both fetal and adult tissues, erythroid-specific expression of the transgene is observed. Transgenic mice have 120-150% greater mature body mass and increased bone mass. The donating investigator also reports transgenic mice have increased dermatological stiffness and toughness. Transgenic mice have a characteristic coat with few guard hairs compared to wildtype littermates. These mice may be useful in studies of bone formation and development, dermatology, and acromegaly.

Development
The human growth hormone gene was modified by replacing the endogenous human promoter with a sheep beta-C globin (HBB) promoter sequence proximal to the 5' human beta-globin locus control region (HS-2). The resulting transgene (termed HS-2+beta^chGH) was injected into the pronucleus of (C57BL/6J x SJL)F1 embryos. Embryos were transferred into pseudopregnant foster mothers. Transgenic offspring (founder line TG420) were bred to C57BL/6J females for approximately 20 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of GH1

005282	NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara/HaraJ
001788	STOCK Tg(Fabp1-GH1)10Bir/J
001400	STOCK Tg(Fabp1-GH1)5Bir/J
001515	STOCK Tg(Fabp1-GH1)7Bir/J

View Strains carrying other alleles of GH1     (4 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Tg(HBB-GH1)420King/0

        involves: C57BL/6J * SJL

• reproductive system phenotype
• reduced female fertility (MGI Ref ID J:109143)
  • hemizygous females are unreliable breeders and mothers
• skin/coat/nails phenotype
• abnormal coat appearance (MGI Ref ID J:109143)
  • coats of hemizygous mice contain fewer guard hairs than wild-type controls'
• abnormal skin condition (MGI Ref ID J:109143)
  • skin of hemizygous mice exhibits unusual toughness or stiffness
• skeleton phenotype
• abnormal bone mineralization (MGI Ref ID J:108828)
  • transgenic mice exhibit delayed mineralization at secondary ossification centers (epiphyses), which at 17 days of age are obvious in bones of controls but poorly formed in transgenic bone, and at 28 days are almost completely fused in control, but not transgenic, bone
• abnormal vertebrae morphology (MGI Ref ID J:108828)
  • vertebrae of transgenic mice appear "blocky" in comparison to control vertebrae
• increased bone density (MGI Ref ID J:108828)
  • radiographic analysis of the caudal vertebrae of transgenic mice reveals greater bone density than in sex-matched control littermates from age 3 weeks, the difference increasing over time to 25-30% by 9 months
• increased cortical bone thickness (MGI Ref ID J:108828)
  • cortical bone thickness of the tibiae of transgenic mice is 20-45% greater than that of sex-matched control littermates
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:108828)
  • radioimmunoassay for plasma levels of human growth hormone detected, on average, 536 ng/ml in 23 day old transgenic mice, which dropped to 228 ng/ml at 33 days and stabilized at ~195 ng/ml by 13 weeks, versus literature control values of 150-160 ng/ml of endogenous growth hormone

Tg(HBB-GH1)420King/?

        involves: C57BL/6J * SJL

• skeleton phenotype
• increased bone strength (MGI Ref ID J:108829)
  • Ca4, Ca5 and Ca6 caudal vertebrae from male transgenic mice can tolerate a 25% greater maximum load (N) in compression at 12 weeks and a 31% greater maximum load at 6 months of age than can vertebrae from age- and sex-matched controls
  • the energy to failure (Nmm) under compression of Ca4, Ca5 and Ca6 caudal vertebrae from male transgenic mice is 30% greater at 12 weeks and 55% greater at 6 months of age than that of vertebrae from age- and sex-matched controls
  • the axial stiffness (N/mm) under compression of Ca4, Ca5 and Ca6 caudal vertebrae from male transgenic mice is 17% greater at 12 weeks and 36% greater at 6 months of age than that of vertebrae from age- and sex-matched wild-type controls
  • Ca4, Ca5 and Ca6 caudal vertebrae from female transgenic mice can tolerate a 32% greater maximum load (N) in compression at 6 months of age than can vertebrae from age- and sex-matched controls; at 12 weeks, the difference was not significant
  • the energy to failure (Nmm) under compression of Ca4, Ca5 and Ca6 caudal vertebrae from female transgenic mice is 26% greater at 6 months of age than that of vertebrae from age- and sex-matched controls; at 12 weeks, the difference was not significant
  • the axial stiffness (N/mm) under compression of Ca4, Ca5 and Ca6 caudal vertebrae from female transgenic mice is 39% greater at 6 months of age than that of vertebrae from age- and sex-matched wild-type controls; at 12 weeks, the difference was not significant

Tg(HBB-GH1)420King/Tg(HBB-GH1)420King

        involves: C57BL/6J * SJL

• reproductive system phenotype
• infertility (MGI Ref ID J:109143)
  • mice homozygous for this transgene are sterile

View Research Applications

Research Applications

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

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Skin Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Research Tools
Dermatology Research
Endocrine Deficiency Research
Immunology and Inflammation Research

HBB related

Hematological Research
Hemoglobin Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(HBB-GH1)420King
Allele Name		transgene insertion 420, Donna King
Allele Type		Transgenic (random, expressed)
Common Name(s)		HS-2 + beta-c hGH; Tg420;
Mutation Made By		Donna King,   N East Ohio Univ Coll of Med (NEOUCOM)
Strain of Origin		(C57BL/6J x SJL/J)F2
Expressed Gene		GH1, growth hormone 1, human
Promoter		HBB, Hemoglobin subunit beta, sheep
		see UniProtKB/Swiss-Prot entry P02075 ( http://ca.expasy.org/cgi-bin/niceprot.pl?HBB_SHEEP )
Molecular Note		The human genomic growth hormone gene, from its transcription initiation site through the 3' untranslated region, was placed under control of the sheep hemoglobin betac promoter joined at its 5' end to a 1.9-kb fragment containing the 5' HS-2 element of the human hemoglobin beta locus control region. Radiolabeled human growth hormone antisense RNA detects transcripts in liver and heart (in the latter presumably from pooled blood) of whole-embryo sections and in bone marrow of sectioned adult tibiae. [MGI Ref ID J:108828]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(HBB-GH1)420King, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Tg(HBB-GH1)420King related

Saban J; Schneider GB; Bolt D; King D. 1996. Erythroid-specific expression of human growth hormone affects bone morphology in transgenic mice. Bone 18(1):47-52. [PubMed: 8717536]  [MGI Ref ID J:108828]

Serrat MA; Vinyard CJ; King D. 2007. Alterations in the mechanical properties and composition of skin in human growth hormone transgenic mice. Connect Tissue Res 48(1):19-26. [PubMed: 17364663]  [MGI Ref ID J:135909]

Steinke B; Patwardhan AG; Havey RM; King D. 1999. Human growth hormone transgene expression increases the biomechanical structural properties of mouse vertebrae. Spine 24(1):1-4. [PubMed: 9921583]  [MGI Ref ID J:108829]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, transgenic males are bred to C57BL/6J or wildtype siblings. The donating investigator reports that transgenic females are unreliable breeders and can exhibit poor fostering of pups. If breeding transgenic females, breed as young as possible and be prepared to foster pups.
Mating System	+/+ sibling x Hemizygote         (Female x Male)

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 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 & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.