STOCK Tg(Cga-LHB/CGB)94Jhn/J

Stock number: 006619
Product name: bLHΒ-CTP
Research areas: Cancer Research, Internal/Organ Research, Reproductive Biology Research

Description

Transgenic females display hypersecretion of luteinizing hormone and other reproductive and endocrine anomalies.

Detailed description

Hemizygous females are not fertile and hemizygous males are sub-fertile. Hemizygotes hypersecrete luteinizing hormone (LH) from pituitary gonadotropes under hypothalamic control. Inclusion of a bovine luteinizing hormone beta (LHB) sequence in the transgene results in a longer hormone half-life. Transgenic females display a range of reproductive and endocrine anomalies, while males are largely phenotypically normal. Transgenic males do not have elevated serum LH or testosterone when compared to wildtype animals, although their testes are significantly smaller. Transgenic females display elevated serum LH, androgens, and estrogens, with subsequent phenotypes including infertility with chronic anovulation and ovarian pathologies ranging from ovarian cysts to strain-dependent granulosa and theca-interstitial cell tumors. Tumors have been noted in mice from age 4 to 9 months. Other major phenotypes include hyperandrogenemia and precocious puberty, defects in uterine receptivity and mid-gestation pregnancy failure, increased oocyte congression failure, adrenocortical hyperfunction, increased central obesity, pituitary adenomas, mammary gland hyperplasia, cancer predisposition, and renal abnormalities (enlarged bladders, dilated ureters, hydronephrosis, nephritis).<br> In humans, LH hypersecretion is implicated in infertility, miscarriages, and development of granulosa cell tumors. This transgenic mouse is a unique model that permits the study of underlying mechanisms of LH toxicity as female transgenic animals display similar reproductive and endocrine pathologies. The female is a model of functional ovarian hyperstimulation, and displays many of the specific endocrine attributes of polycystic ovarian syndrome (PCOS), granulosa cell tumor formation, and central precocious puberty.

Development

The transgene consists of the entire bovine luteinizing hormone beta (LHB) cDNA fused in-frame to the last 87 bp of the human chorionic gonadotropin beta gene (CGB) encoding the carboxy terminal peptide (CTP), whose expression is driven by the bovine glycoprotein hormone alpha (CGA) promoter (positions -315 to +45). The construct was initially injected into C57BL/6 x SJL F1 hybrid embryos, but foundation animals were crossed subsequently to outbred CF-1 females for more than ten generations.

Allele

Symbol: Tg(Cga-LHB/CGB)94Jhn
Name: transgene insertion 94, John H Nilson
MGI accession ID: MGI:2446075
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Cga-LHB/CGB)94Jhn
Marker name: transgene insertion 94, John H Nilson
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: LHB,luteinizing hormone beta polypeptide,bovine; CGB3,chorionic gonadotropin subunit beta 3,human
Molecular note: The transgene contains the entire bovine luteinizing hormone beta (LHB) cDNA fused to 87 bp encoding the c-terminal peptide (CTP) of the human chorionic gonadotropin beta subunit (CGB). The bovine glycoprotein hormone alpha subunit (CGA) promoter (positions -315 to +45) was used to drive expression in gonadotropes. Immunohistochemical analysis confirmed both LHB and CTP expression in the pituitaries.