C57BL/6-Tg(Dmp1-PTH1R*H223R)564Btm/Mmjax

Stock number: 032017
Product name: DMP1-caPTHR1
Strain synonyms: DMP1-8kb-caPTRH1
Research areas: Endocrine Deficiency Research, Internal/Organ Research

Description

DMP1-caPTHR1 mice express a constitutively active human parathyroid hormone 1 receptor gene in osteocytes. Transgenic mice develop increased bone mass and bone remodeling. This transgenic strain may be useful in studying hormonal control of skeletal homeostasis.

Detailed description

Parathyroid hormone 1 receptor (PTHR1) functions as a receptor for parathyroid hormone and parathyroid hormone-like hormone. Mutations in this gene are associated with several types of chrondodysplasia.

DMP1-caPTHR1 mice have expression of a constitutively active human PTHR1 (caPTHR1) directed to osteocytes by the mouse dentin matrix protein 1 promoter (Dmp1). caPTHR1 expression is detected in bone tissues (vertebrae and tibia), but not in kidney, liver, spleen, heart or brain.

Transgenic mice develop a progressive increase in bone mass beginning at 4 weeks of age. Femoral bone marrow density is 63% higher than controls at 8 weeks and 109% higher at 24 weeks. Increased numbers of osteoclasts and osteoblasts result in an increased rate of bone remodeling. The increase in osteoblasts is associated with a decrease in osteoblast apoptosis.

Mice hemizygous for the transgene are viable and fertile.

This transgenic strain may be useful in studies related to hormonal control of skeletal homeostasis.

Development

The DMP1-caPTHR1 transgene was designed with a mouse Dmp1 (dentin matrix protein 1) promoter (8kb of the 5' flanking region, the first exon, the first intron and 17bp of exon 2) directing expression of a modified human PTHR1 (parathyroid hormone 1 receptor) gene, followed by a rabbit beta-globin polyA sequence. This PTHR1 sequence contains a histidine-to-arginine substitution at residue 223 (H223R or c.668A>G); the substitution results in constitutively active expression of PTHR1 (caPTHR1). The linearized construct was microinjected into fertilized C57BL/6 oocytes. Founder line 564 was established and the colony maintained on the C57BL/6NHsd background. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Allele

Symbol: Tg(Dmp1-PTH1R*H223R)564Btm
Name: transgene insertion 564, Teresita Bellido
MGI accession ID: MGI:6151434
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: DMP1-caPTHR1
Marker symbol: Tg(Dmp1-PTH1R*H223R)564Btm
Marker name: transgene insertion 564, Teresita Bellido
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: PTH1R,parathyroid hormone 1 receptor,human
Site of expression: Osteocytes
Molecular note: The transgenic construct contains a mouse Dmp1 promoter, including 8kb of the 5' flanking region, the first exon, the first intron, and 17 bp of exon 2, followed by a modified human PTHR1 gene, and a rabbit beta-globin polyA sequence. PTHR1 contains a histidine to arginine substitution at residue 223 (H223R or c.668A>G); the substitution results in constitutively active expression of PTHR1.