Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex-specific reproductive disease

Jesse J. Savage, Rachel D. Mullen, Kyle W. Sloop, Stephanie C. Colvin, Sally A. Camper, Craig L. Franklin, Simon Rhodes

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit (αGSU) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male αGSU-LHX3a and αGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female αGSU-LHX3a and αGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, αGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology.

Original languageEnglish
Pages (from-to)105-117
Number of pages13
JournalJournal of Cellular Physiology
Volume212
Issue number1
DOIs
StatePublished - Jul 2007

Fingerprint

Transgenic Mice
Glycoproteins
Protein Isoforms
Transcription Factors
Genes
beta-Galactosidase
Animals
Deficiency Diseases
Uremia
Physiology
Gonadal Steroid Hormones
Neurology
Pituitary Gland
Regulator Genes
Gonadotropins
Nervous System
Transcriptional Activation
Fertility
Proteins
Hormones

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary : Effects on the gonadotrope axis and sex-specific reproductive disease. / Savage, Jesse J.; Mullen, Rachel D.; Sloop, Kyle W.; Colvin, Stephanie C.; Camper, Sally A.; Franklin, Craig L.; Rhodes, Simon.

In: Journal of Cellular Physiology, Vol. 212, No. 1, 07.2007, p. 105-117.

Research output: Contribution to journalArticle

Savage, Jesse J. ; Mullen, Rachel D. ; Sloop, Kyle W. ; Colvin, Stephanie C. ; Camper, Sally A. ; Franklin, Craig L. ; Rhodes, Simon. / Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary : Effects on the gonadotrope axis and sex-specific reproductive disease. In: Journal of Cellular Physiology. 2007 ; Vol. 212, No. 1. pp. 105-117.
@article{a7ab878029d347a6b7ad3bfd25dc039d,
title = "Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex-specific reproductive disease",
abstract = "The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit (αGSU) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male αGSU-LHX3a and αGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female αGSU-LHX3a and αGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, αGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology.",
author = "Savage, {Jesse J.} and Mullen, {Rachel D.} and Sloop, {Kyle W.} and Colvin, {Stephanie C.} and Camper, {Sally A.} and Franklin, {Craig L.} and Simon Rhodes",
year = "2007",
month = "7",
doi = "10.1002/jcp.21010",
language = "English",
volume = "212",
pages = "105--117",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary

T2 - Effects on the gonadotrope axis and sex-specific reproductive disease

AU - Savage, Jesse J.

AU - Mullen, Rachel D.

AU - Sloop, Kyle W.

AU - Colvin, Stephanie C.

AU - Camper, Sally A.

AU - Franklin, Craig L.

AU - Rhodes, Simon

PY - 2007/7

Y1 - 2007/7

N2 - The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit (αGSU) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male αGSU-LHX3a and αGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female αGSU-LHX3a and αGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, αGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology.

AB - The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit (αGSU) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male αGSU-LHX3a and αGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female αGSU-LHX3a and αGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, αGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology.

UR - http://www.scopus.com/inward/record.url?scp=34249880146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249880146&partnerID=8YFLogxK

U2 - 10.1002/jcp.21010

DO - 10.1002/jcp.21010

M3 - Article

C2 - 17311285

AN - SCOPUS:34249880146

VL - 212

SP - 105

EP - 117

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 1

ER -