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

Former Names B6.SJL-Tg(HBB-GH1)420King/J    (Changed: 06-OCT-11 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Hemizygote         (Female x Male)   03-OCT-08 Species laboratory mouse Generation ?+N1p Generation Definitions   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)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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
  • hemizygous females are unreliable breeders and mothers   (MGI Ref ID J:109143)
• skeleton phenotype
• abnormal bone mineralization
  • 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   (MGI Ref ID J:108828)
• abnormal vertebrae morphology
  • vertebrae of transgenic mice appear "blocky" in comparison to control vertebrae   (MGI Ref ID J:108828)
• increased bone mineral density
  • 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   (MGI Ref ID J:108828)
• increased compact bone thickness
  • cortical bone thickness of the tibiae of transgenic mice is 20-45% greater than that of sex-matched control littermates   (MGI Ref ID J:108828)
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • 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   (MGI Ref ID J:108828)
• integument phenotype
• abnormal coat appearance
  • coats of hemizygous mice contain fewer guard hairs than wild-type controls'   (MGI Ref ID J:109143)
• abnormal skin condition
  • skin of hemizygous mice exhibits unusual toughness or stiffness   (MGI Ref ID J:109143)

Tg(HBB-GH1)420King/?

        involves: C57BL/6J * SJL

• skeleton phenotype
• increased bone strength
  • 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   (MGI Ref ID J:108829)
  • 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   (MGI Ref ID J:108829)
  • 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   (MGI Ref ID J:108829)
  • 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   (MGI Ref ID J:108829)
  • 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   (MGI Ref ID J:108829)
  • 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   (MGI Ref ID J:108829)

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

        involves: C57BL/6J * SJL

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

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

Genes & Alleles

Gene & Allele Information provided by MGI

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
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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

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, 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)   03-OCT-08

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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