Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development

Martin M. Matzuk, T. Rajendra Kumar, Weinian Shou, Katherine A. Coerver, Anthony L. Lau, Richard R. Behringer, Milton J. Finegold

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

With the advent of gene targeting in pluripotent mouse embryonic stem cells, it is now possible to modify the mammalian genome to generate mutant strains of mice with precise genetic mutations. The major goal of my laboratory is to generate transgenic mice to use as physiologic models to study mammalian reproduction and development. The initial focus of our research has been to generate mice deficient in inhibins, activins, activin binding proteins (i.e., follistatin), and activin receptors (i.e., activin receptor type II) to understand their interactions and roles in the hypothalamic-pituitary-gonadal axis and mammalian development. Inhibins and activins, dimenc members of the TGF-β superfamily, were discovered due to their role in pituitary follicle stimulating hormone homeostasis. However, these proteins have later been shown to have diverse endocrine, paracrine, and autocrine functions. Activins have been shown to mediate their signals through type I and type II serine/threonine kinase receptors. The high interspecies conservation of activins, inhibins, and activin receptors and the universal presence of activins in mammals, birds, amphibians, and fish suggest an evolutionarily conserved role of these proteins in animal development Our initial studies have demonstrated a tumor suppressor role of inhibin in the gonads and adrenals and have also suggested a role of activins in cancer cachexia-like syndrome. To further study the gonadal tumor development and the cancer cachexia-like syndrome in these mice, we have begun to generate mice with multiple genetic alterations (e.g., mice deficient in both inhibin and Mullerian inhibiting substance). We have also generated mice deficient in other components of this complex system (e.g., activin βA, activin receptor type II, follistatin). Analysis of these transgenic mutant models has aided our overall understanding of the critical roles these proteins play in the development of the reproductive system, in the modulation of the endocrine milieu that regulates reproductive function, and in mammalian development.

Original languageEnglish (US)
Pages (from-to)123-154
Number of pages32
JournalRecent Progress in Hormone Research
Volume51
StatePublished - Dec 1 1996

Fingerprint

Activins
Inhibins
Reproduction
Carcinogenesis
Activin Receptors
Follistatin
Cachexia
Neoplasms
Type II Activin Receptors
Mutant Strains Mice
Anti-Mullerian Hormone
Proteins
Pituitary Hormones
Gene Targeting
Protein-Serine-Threonine Kinases
Gonads
Follicle Stimulating Hormone
Amphibians
Transgenic Mice
Birds

ASJC Scopus subject areas

  • Endocrinology

Cite this

Matzuk, M. M., Kumar, T. R., Shou, W., Coerver, K. A., Lau, A. L., Behringer, R. R., & Finegold, M. J. (1996). Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development. Recent Progress in Hormone Research, 51, 123-154.

Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development. / Matzuk, Martin M.; Kumar, T. Rajendra; Shou, Weinian; Coerver, Katherine A.; Lau, Anthony L.; Behringer, Richard R.; Finegold, Milton J.

In: Recent Progress in Hormone Research, Vol. 51, 01.12.1996, p. 123-154.

Research output: Contribution to journalArticle

Matzuk, MM, Kumar, TR, Shou, W, Coerver, KA, Lau, AL, Behringer, RR & Finegold, MJ 1996, 'Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development', Recent Progress in Hormone Research, vol. 51, pp. 123-154.
Matzuk, Martin M. ; Kumar, T. Rajendra ; Shou, Weinian ; Coerver, Katherine A. ; Lau, Anthony L. ; Behringer, Richard R. ; Finegold, Milton J. / Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development. In: Recent Progress in Hormone Research. 1996 ; Vol. 51. pp. 123-154.
@article{b1d6ffe9320c4cef860ab939482cf9da,
title = "Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development",
abstract = "With the advent of gene targeting in pluripotent mouse embryonic stem cells, it is now possible to modify the mammalian genome to generate mutant strains of mice with precise genetic mutations. The major goal of my laboratory is to generate transgenic mice to use as physiologic models to study mammalian reproduction and development. The initial focus of our research has been to generate mice deficient in inhibins, activins, activin binding proteins (i.e., follistatin), and activin receptors (i.e., activin receptor type II) to understand their interactions and roles in the hypothalamic-pituitary-gonadal axis and mammalian development. Inhibins and activins, dimenc members of the TGF-β superfamily, were discovered due to their role in pituitary follicle stimulating hormone homeostasis. However, these proteins have later been shown to have diverse endocrine, paracrine, and autocrine functions. Activins have been shown to mediate their signals through type I and type II serine/threonine kinase receptors. The high interspecies conservation of activins, inhibins, and activin receptors and the universal presence of activins in mammals, birds, amphibians, and fish suggest an evolutionarily conserved role of these proteins in animal development Our initial studies have demonstrated a tumor suppressor role of inhibin in the gonads and adrenals and have also suggested a role of activins in cancer cachexia-like syndrome. To further study the gonadal tumor development and the cancer cachexia-like syndrome in these mice, we have begun to generate mice with multiple genetic alterations (e.g., mice deficient in both inhibin and Mullerian inhibiting substance). We have also generated mice deficient in other components of this complex system (e.g., activin βA, activin receptor type II, follistatin). Analysis of these transgenic mutant models has aided our overall understanding of the critical roles these proteins play in the development of the reproductive system, in the modulation of the endocrine milieu that regulates reproductive function, and in mammalian development.",
author = "Matzuk, {Martin M.} and Kumar, {T. Rajendra} and Weinian Shou and Coerver, {Katherine A.} and Lau, {Anthony L.} and Behringer, {Richard R.} and Finegold, {Milton J.}",
year = "1996",
month = "12",
day = "1",
language = "English (US)",
volume = "51",
pages = "123--154",
journal = "Recent Progress in Hormone Research",
issn = "0079-9963",
publisher = "The Endocrine Society",

}

TY - JOUR

T1 - Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development

AU - Matzuk, Martin M.

AU - Kumar, T. Rajendra

AU - Shou, Weinian

AU - Coerver, Katherine A.

AU - Lau, Anthony L.

AU - Behringer, Richard R.

AU - Finegold, Milton J.

PY - 1996/12/1

Y1 - 1996/12/1

N2 - With the advent of gene targeting in pluripotent mouse embryonic stem cells, it is now possible to modify the mammalian genome to generate mutant strains of mice with precise genetic mutations. The major goal of my laboratory is to generate transgenic mice to use as physiologic models to study mammalian reproduction and development. The initial focus of our research has been to generate mice deficient in inhibins, activins, activin binding proteins (i.e., follistatin), and activin receptors (i.e., activin receptor type II) to understand their interactions and roles in the hypothalamic-pituitary-gonadal axis and mammalian development. Inhibins and activins, dimenc members of the TGF-β superfamily, were discovered due to their role in pituitary follicle stimulating hormone homeostasis. However, these proteins have later been shown to have diverse endocrine, paracrine, and autocrine functions. Activins have been shown to mediate their signals through type I and type II serine/threonine kinase receptors. The high interspecies conservation of activins, inhibins, and activin receptors and the universal presence of activins in mammals, birds, amphibians, and fish suggest an evolutionarily conserved role of these proteins in animal development Our initial studies have demonstrated a tumor suppressor role of inhibin in the gonads and adrenals and have also suggested a role of activins in cancer cachexia-like syndrome. To further study the gonadal tumor development and the cancer cachexia-like syndrome in these mice, we have begun to generate mice with multiple genetic alterations (e.g., mice deficient in both inhibin and Mullerian inhibiting substance). We have also generated mice deficient in other components of this complex system (e.g., activin βA, activin receptor type II, follistatin). Analysis of these transgenic mutant models has aided our overall understanding of the critical roles these proteins play in the development of the reproductive system, in the modulation of the endocrine milieu that regulates reproductive function, and in mammalian development.

AB - With the advent of gene targeting in pluripotent mouse embryonic stem cells, it is now possible to modify the mammalian genome to generate mutant strains of mice with precise genetic mutations. The major goal of my laboratory is to generate transgenic mice to use as physiologic models to study mammalian reproduction and development. The initial focus of our research has been to generate mice deficient in inhibins, activins, activin binding proteins (i.e., follistatin), and activin receptors (i.e., activin receptor type II) to understand their interactions and roles in the hypothalamic-pituitary-gonadal axis and mammalian development. Inhibins and activins, dimenc members of the TGF-β superfamily, were discovered due to their role in pituitary follicle stimulating hormone homeostasis. However, these proteins have later been shown to have diverse endocrine, paracrine, and autocrine functions. Activins have been shown to mediate their signals through type I and type II serine/threonine kinase receptors. The high interspecies conservation of activins, inhibins, and activin receptors and the universal presence of activins in mammals, birds, amphibians, and fish suggest an evolutionarily conserved role of these proteins in animal development Our initial studies have demonstrated a tumor suppressor role of inhibin in the gonads and adrenals and have also suggested a role of activins in cancer cachexia-like syndrome. To further study the gonadal tumor development and the cancer cachexia-like syndrome in these mice, we have begun to generate mice with multiple genetic alterations (e.g., mice deficient in both inhibin and Mullerian inhibiting substance). We have also generated mice deficient in other components of this complex system (e.g., activin βA, activin receptor type II, follistatin). Analysis of these transgenic mutant models has aided our overall understanding of the critical roles these proteins play in the development of the reproductive system, in the modulation of the endocrine milieu that regulates reproductive function, and in mammalian development.

UR - http://www.scopus.com/inward/record.url?scp=0029721748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029721748&partnerID=8YFLogxK

M3 - Article

C2 - 8701077

AN - SCOPUS:0029721748

VL - 51

SP - 123

EP - 154

JO - Recent Progress in Hormone Research

JF - Recent Progress in Hormone Research

SN - 0079-9963

ER -