JAX Mouse Strain Datasheet - 006619

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

Stock No:: 006619 |; bLHΒ-CTP

Transgenic

Cryo Recovery

Overview

Also Known As: bLHΒ-CTP

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

Donating Investigator

John Nilson, Washington State University

Genetic overview

Genetic Background	Generation

Tg(Cga-LHB/CGB)94Jhn

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Cancer Research
Internal/Organ Research
Reproductive Biology Research

View All Research Applications

Base Price

Starting at:

$2,625.00 Domestic price Cryo Recovery

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Details

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.

Expression Data

Expressed Gene	CGB3, chorionic gonadotropin beta subunit 3, human
Expressed Gene	LHB, luteinizing hormone beta polypeptide, bovine
Site of Expression

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Risma KA; Clay CM; Nett TM; Wagner T; Yun J; Nilson JH. 1995. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. Proc Natl Acad Sci U S A 92(5):1322-6. PubMed: 7877975 MGI: J:55157

View All References

Genetics

Tg(Cga-LHB/CGB)94Jhn

Allele Symbol: Tg(Cga-LHB/CGB)94Jhn

Allele Name	transgene insertion 94, John H Nilson
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	LH-CTP; LHbeta-CTP; Tg(bLHbeta-CTP)94Jhn; Tg-LHbeta
Gene Symbol and Name	Tg(Cga-LHB/CGB)94Jhn, transgene insertion 94, John H Nilson
Gene Synonym(s)	LH-CTP; LHbeta-CTP; LHbetaCTP; Tg(bLHbeta-CTP)94Jhn; Tg(bLHbeta-CTP)94Jhn; Tg-LHbeta
Promoter	Cga, glycoprotein hormones, alpha polypeptide, bovine
Expressed Gene	CGB3, chorionic gonadotropin beta subunit 3, human
Expressed Gene	LHB, luteinizing hormone beta polypeptide, bovine
Strain of Origin	(C57BL/6 x SJL)F1
Chromosome	UN
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.
Mutations Made By	John Nilson, Washington State University

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Cancer Research
- Increased Tumor Incidence
  - Gonadal Tumors
  - Gonadal Tumors: ovarian
Internal/Organ Research
- Kidney Defects
Reproductive Biology Research
- Fertility Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(Cga-LHB/CGB)94Jhn/?
involves: C57BL/6 * SJL

reproductive system phenotype

anovulation
- 12-16 week old female mice fail to ovulate
- female mice fail to ovulate even when ovulation is tried to be forced through pseudopregnancy

delayed male fertility
- some males breed after prolonged delays

enlarged ovary
- progesterone levels are elevated in these mice
- some of the females have enlarged ovaries that are packed with corpora lutea

impaired luteal cell differentiation
- luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls

increased ovary tumor incidence
- a subset of transgenic females develop ovarian granulose and theca-interstitial cell tumors by 4-8 months of age
- these tumors contain varying amounts of other stromal cells and have an increased blood supply

ovary cysts
- cystic ovaries have increased blood flow to the tissue
- some mice have numerous cysts in their ovaries that are hemorrhagic or fluid filled and derived from both follicular and luteal tissue
- testosterone and estradiol levels are elevated in these mice

reduced female fertility
- only 1 female of 9 that mated multiple times was able to produce a litter

reduced male fertility
- male mice have reduced fertility with some males never breeding and others breeding after prolonged delays

small testis
- testes in transgenic males is significantly smaller than in controls

neoplasm

increased ovary tumor incidence
- a subset of transgenic females develop ovarian granulose and theca-interstitial cell tumors by 4-8 months of age
- these tumors contain varying amounts of other stromal cells and have an increased blood supply

renal/urinary system phenotype

dilated ureter
- about 25% of infertile females have dilated ureters associated with hydronephrosis of the kidneys

distended urinary bladder
- about 25% of infertile females have enlarged bladders associated with hydronephrosis of the kidneys

hydronephrosis
- about 25% of infertile females have hydronephrosis of the kidneys
- in some mice the hydronephropathy is complicated by acute pyelonephritis whereas others have chronic interstitial nephritis

pyelonephritis
- in some mice the hydronephropathy is complicated by acute pyelonephritis

tubulointerstitial nephritis
- some mice develop chronic interstitial nephritis

homeostasis/metabolism phenotype

increased circulating luteinizing hormone level
- serum LH levels for female mice are elevated at 39.7 ng/ml compared to 2.7 ng/ml for littermate controls

increased circulating progesterone level
- transgenic females that have enlarged ovaries also have vastly elevated progesterone levels

endocrine/exocrine gland phenotype

abnormal adrenocortical cell morphology
- cells expressing markers of gonadal origin reside in the subcapsular zone of the adrenal cortex where stem cells normally reside
- these cells express high levels of phosphorylated Smad3

enlarged ovary
- progesterone levels are elevated in these mice
- some of the females have enlarged ovaries that are packed with corpora lutea

impaired luteal cell differentiation
- luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls

increased ovary tumor incidence
- a subset of transgenic females develop ovarian granulose and theca-interstitial cell tumors by 4-8 months of age
- these tumors contain varying amounts of other stromal cells and have an increased blood supply

ovary cysts
- cystic ovaries have increased blood flow to the tissue
- some mice have numerous cysts in their ovaries that are hemorrhagic or fluid filled and derived from both follicular and luteal tissue
- testosterone and estradiol levels are elevated in these mice

small testis
- testes in transgenic males is significantly smaller than in controls

immune system phenotype

pyelonephritis
- in some mice the hydronephropathy is complicated by acute pyelonephritis

tubulointerstitial nephritis
- some mice develop chronic interstitial nephritis

cellular phenotype

impaired luteal cell differentiation
- luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls

References

Risma KA; Clay CM; Nett TM; Wagner T; Yun J; Nilson JH. 1995. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. Proc Natl Acad Sci U S A 92(5):1322-6. PubMed: 7877975 MGI: J:55157

Additional - Tg(Cga-LHB/CGB)94Jhn related

Basham KJ; Hung HA; Lerario AM; Hammer GD. 2016. Mouse models of adrenocortical tumors. Mol Cell Endocrinol 421:82-97. PubMed: 26678830 MGI: J:236509
Beuschlein F; Looyenga BD; Bleasdale SE; Mutch C; Bavers DL; Parlow AF; Nilson JH; Hammer GD. 2003. Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice. Mol Cell Biol 23(11):3951-64. PubMed: 12748296 MGI: J:83561
Casadesus G; Milliken EL; Webber KM; Bowen RL; Lei Z; Rao CV; Perry G; Keri RA; Smith MA. 2007. Increases in luteinizing hormone are associated with declines in cognitive performance. Mol Cell Endocrinol 269(1-2):107-11. PubMed: 17376589 MGI: J:126509
Couse JF; Yates MM; Rodriguez KF; Johnson JA; Poirier D; Korach KS. 2006. The intraovarian actions of estrogen receptor-alpha are necessary to repress the formation of morphological and functional Leydig-like cells in the female gonad. Endocrinology 147(8):3666-78. PubMed: 16627580 MGI: J:111680
Couse JF; Yates MM; Sanford R; Nyska A; Nilson JH; Korach KS. 2004. Formation of cystic ovarian follicles associated with elevated luteinizing hormone requires estrogen receptor-beta. Endocrinology 145(10):4693-702. PubMed: 15231698 MGI: J:92628
Flaws JA; Abbud R; Mann RJ; Nilson JH; Hirshfield AN. 1997. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Reprod 57(5):1233-7. PubMed: 9369192 MGI: J:163516
Hodges CA; Ilagan A; Jennings D; Keri R; Nilson J; Hunt PA. 2002. Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation. Hum Reprod 17(5):1171-80. PubMed: 11980735 MGI: J:115500
Keri RA; Lozada KL; Abdul-Karim FW; Nadeau JH; Nilson JH. 2000. Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition. Proc Natl Acad Sci U S A 97(1):383-7. PubMed: 10618427 MGI: J:59366
Landis MD; Seachrist DD; Abdul-Karim FW; Keri RA. 2006. Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors. Oncogene 25(23):3325-34. PubMed: 16434967 MGI: J:112325
Looyenga BD; Hammer GD. 2007. Genetic removal of smad3 from inhibin-null mice attenuates tumor progression by uncoupling extracellular mitogenic signals from the cell cycle machinery. Mol Endocrinol 21(10):2440-57. PubMed: 17652186 MGI: J:125349
Looyenga BD; Wiater E; Vale W; Hammer GD. 2010. Inhibin-A antagonizes TGFbeta2 signaling by down-regulating cell surface expression of the TGFbeta coreceptor betaglycan. Mol Endocrinol 24(3):608-20. PubMed: 20160125 MGI: J:157913
Lyubarsky AL; Chen C; Simon MI; Pugh EN Jr. 2000. Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. J Neurosci 20(6):2209-17. PubMed: 10704496 MGI: J:60964
Mann RJ; Keri RA; Nilson JH. 2003. Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. Recent Prog Horm Res 58:343-75. PubMed: 12795427 MGI: J:84511
Mann RJ; Keri RA; Nilson JH. 1999. Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure. Endocrinology 140(6):2592-601. PubMed: 10342846 MGI: J:66176
Mikola M; Kero J; Nilson JH; Keri RA; Poutanen M; Huhtaniemi I. 2003. High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene. Oncogene 22(21):3269-78. PubMed: 12761497 MGI: J:83778
Milliken EL; Ameduri RK; Landis MD; Behrooz A; Abdul-Karim FW; Keri RA. 2002. Ovarian Hyperstimulation by LH Leads to Mammary Gland Hyperplasia and Cancer Predisposition in Transgenic Mice. Endocrinology 143(9):3671-80. PubMed: 12193583 MGI: J:78490
Milliken EL; Lozada KL; Johnson E; Landis MD; Seachrist DD; Whitten I; Sutton AL; Abdul-Karim FW; Keri RA. 2008. Ovarian hyperstimulation induces centrosome amplification and aneuploid mammary tumors independently of alterations in p53 in a transgenic mouse model of breast cancer. Oncogene 27(12):1759-66. PubMed: 17891171 MGI: J:135510
Milliken EL; Zhang X; Flask C; Duerk JL; Macdonald PN; Keri RA. 2005. EB1089, a vitamin D receptor agonist, reduces proliferation and decreases tumor growth rate in a mouse model of hormone-induced mammary cancer. Cancer Lett 229(2):205-15. PubMed: 16115727 MGI: J:101899
Mohammad HP; Abbud RA; Parlow AF; Lewin JS; Nilson JH. 2003. Targeted overexpression of luteinizing hormone causes ovary-dependent functional adenomas restricted to cells of the Pit-1 lineage. Endocrinology 144(10):4626-36. PubMed: 12960102 MGI: J:85766
Nilson JH; Abbud RA; Keri RA; Quirk CC. 2000. Chronic hypersecretion of luteinizing hormone in transgenic mice disrupts both ovarian and pituitary function, with some effects modified by the genetic background Recent Prog Horm Res 55:69-89; discussion 89-91. PubMed: 11036934 MGI: J:65359
Owens GE; Keri RA; Nilson JH. 2002. Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome. Mol Endocrinol 16(6):1230-42. PubMed: 12040011 MGI: J:76875
Risma KA; Hirshfield AN; Nilson JH. 1997. Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology. Endocrinology 138(8):3540-7. PubMed: 9231809 MGI: J:66175

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Also Known As: bLHΒ-CTP

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Cga-LHB/CGB)94Jhn

Allele Symbol: Tg(Cga-LHB/CGB)94Jhn

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Cga-LHB/CGB)94Jhn/?involves: C57BL/6 * SJL

reproductive system phenotype

neoplasm

renal/urinary system phenotype

homeostasis/metabolism phenotype

endocrine/exocrine gland phenotype

immune system phenotype

cellular phenotype

References

Additional - Tg(Cga-LHB/CGB)94Jhn related

Genotyping Protocols

Breeding Considerations

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

RELATED PRODUCTS AND SERVICES

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Cga-LHB/CGB)94Jhn/?
involves: C57BL/6 * SJL