FVB/N-Tg(PTH-CCND1)PC2Anar/J

Stock number: 028218
Product name: PTH–cyclin D1, line PC2
Strain synonyms: PTH-D1
Research areas: Cancer Research, Endocrine Deficiency Research, Research Tools

Description

These PTH–cyclin D1, line PC2 transgenic mice express a transgene containing the human cyclin D1 gene (CCND1) and develop chronic biochemical hyperparathyroidism and enlarged, hypercellular parathyroid glands.

Detailed description

These transgenic mice overexpress the human cyclin D1 gene (CCND1) in the parathyroid glands under the direction of the human PTH gene regulatory elements. Founder line PC2 has an estimated 11 copies of the transgene. The transgene fusion mimics an inversion found in some human parathyroid adenomas. Higher levels of serum calcium and parathyroid hormone are detectable as early as 6 to 9 months of age in transgenic mice, with the elevated levels becoming significant by 10 months of age. By 5 months of age, transgenic mice exhibit increased parathyroid cell proliferation rates, and by 5-6 months increased parathyroid gland size and hypercellularity is observed, sometimes with features suggestive of adenomas. Transgenic mice also have decreased bone volume, evidence of increased bone turnover, increased numbers of osteoclasts and bone formation in the calvaria, as well as fewer calcium receptors, which is similar to features observed in human hyperparathyroidism. Mice that are hemizygous for the transgene are viable and fertile. The Donating Investigator has not attempted to make the strain homozygous; it is not known if homozygotes are viable.

Development

A transgenic construct designed by Dr. Andrew Arnold (University of Connecticut School of Medicine, Farmington, Connecticut) containing a 16kb genomic fragment of the human CCND1 gene (all exons and introns, 1.1kb 5'-flanking region, and 1kb 3'-flanking region) under the control of the human PTH gene promoter (approximately 5 kb of upstream, 5'-regulatory region, and the first 66 bp of untranslated/non-coding exon 1), was injected into the pronuclei of fertilized FVB/N mouse eggs. Founder line PC2, which has an estimated 11 copies of the transgene, was subsequently established. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Tg(PTH-CCND1)PC2Anar
Name: transgene insertion PC2, Andrew Arnold
MGI accession ID: MGI:3844257
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: PC2; Tg(PTH-CCND1)2Anar
Marker symbol: Tg(PTH-CCND1)PC2Anar
Marker name: transgene insertion PC2, Andrew Arnold
Marker synonyms: PC2; Tg(PTH-CCND1)2Anar
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: CCND1,cyclin D1,human
Site of expression: Parathyroid glands
Molecular note: 5.2 kb of the upstream regulatory region the human PTH gene was used to drive long range tissue specific expression of the full-length 16 kb human cyclin D1 gene in conjunction with its own promoter elements for basal expression. This fusion mimics an inversion found in some human parathyroid adenomas. Three lines were created (1, 2, and 4 with 3, 11, and 15 copies of the transgene, respectively). Line 2 was selected as the representative line.