Development of a transgenic mouse that overexpresses a novel product of the growth hormone-releasing hormone gene

S. Fang, R. Steinmetz, D. W. King, P. Zeng, C. Vogelweid, S. Cooper, G. Hangcoc, H. E. Broxmeyer, O. H. Pescovitz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The GH-releasing hormone (GHRH) precursor molecule contains a 30-amino acid C-terminal region that has been designated GHRH-related peptide (GHRH-RP). To begin to understand the physiological role of GHRH-RP, transgenic (Tg) mice that constituitively express this peptide were developed. To generate these mice, a transgene (SS-RP) was constructed by overlap primer extension PCR. This transgene, under the control of the mouse phosphoglycerate kinase gene, selectively expresses GHRH-RP, but not GHRH. Western blot analysis confirmed that the transgene produces GHRH-RP. Animals were evaluated for the effect of excess GHRH-RP on growth, fertility, behavior, stem cell factor (SCF) expression, and hematopoiesis. Northern blot and RT-PCR were used to demonstrate ubiquitous expression of the transgene in tissues from GHRH-RP Tg animals. These tissues also had marked overexpression of SCF messenger RNA compared with controls. Tg animals had significantly increased cell cycling for granulocyte-macrophage, erythroid, and multilineage progenitor cells. Transgenic animals did not differ from control mice in their growth, fertility, or behavior. These findings demonstrate, for the first time, that in vivo the C-terminal peptide of the pro-GHRH molecule is a biologically active peptide that is capable of stimulating the expression of SCF and hematopoiesis in vivo and suggests that GHRH-RP may play a role in normal blood cell development.

Original languageEnglish (US)
Pages (from-to)1377-1383
Number of pages7
JournalEndocrinology
Volume141
Issue number4
DOIs
StatePublished - Jan 1 2000

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Growth Hormone-Releasing Hormone
Transgenic Mice
Hormones
Genes
Transgenes
Genetically Modified Animals
Stem Cell Factor
Hematopoiesis
Peptides
Fertility
Phosphoglycerate Kinase
Polymerase Chain Reaction
Erythroid Precursor Cells
Peptide Hormones
Growth
Granulocytes
Northern Blotting
Blood Cells
Western Blotting
Macrophages

ASJC Scopus subject areas

  • Endocrinology

Cite this

Fang, S., Steinmetz, R., King, D. W., Zeng, P., Vogelweid, C., Cooper, S., ... Pescovitz, O. H. (2000). Development of a transgenic mouse that overexpresses a novel product of the growth hormone-releasing hormone gene. Endocrinology, 141(4), 1377-1383. https://doi.org/10.1210/endo.141.4.7422

Development of a transgenic mouse that overexpresses a novel product of the growth hormone-releasing hormone gene. / Fang, S.; Steinmetz, R.; King, D. W.; Zeng, P.; Vogelweid, C.; Cooper, S.; Hangcoc, G.; Broxmeyer, H. E.; Pescovitz, O. H.

In: Endocrinology, Vol. 141, No. 4, 01.01.2000, p. 1377-1383.

Research output: Contribution to journalArticle

Fang, S, Steinmetz, R, King, DW, Zeng, P, Vogelweid, C, Cooper, S, Hangcoc, G, Broxmeyer, HE & Pescovitz, OH 2000, 'Development of a transgenic mouse that overexpresses a novel product of the growth hormone-releasing hormone gene', Endocrinology, vol. 141, no. 4, pp. 1377-1383. https://doi.org/10.1210/endo.141.4.7422
Fang, S. ; Steinmetz, R. ; King, D. W. ; Zeng, P. ; Vogelweid, C. ; Cooper, S. ; Hangcoc, G. ; Broxmeyer, H. E. ; Pescovitz, O. H. / Development of a transgenic mouse that overexpresses a novel product of the growth hormone-releasing hormone gene. In: Endocrinology. 2000 ; Vol. 141, No. 4. pp. 1377-1383.
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