scholarly journals Overexpression of Parathyroid Hormone-related Protein in the Pancreatic Islets of Transgenic Mice Causes Islet Hyperplasia, Hyperinsulinemia, and Hypoglycemia

1996 ◽  
Vol 271 (2) ◽  
pp. 1200-1208 ◽  
Author(s):  
Rupangi C. Vasavada ◽  
Christi Cavaliere ◽  
A. Joseph D'Ercole ◽  
Pamela Dann ◽  
William J. Burtis ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Transgenic Mice ◽  
Pancreatic Islets ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Islet Hyperplasia

scholarly journals Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes

2001 ◽  
Vol 171 (3) ◽  
pp. 403-416 ◽  
Author(s):  
ME Dunbar ◽  
P Dann ◽  
CW Brown ◽  
J Van Houton ◽  
B Dreyer ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Transgenic Mice ◽  
Mammary Development ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Epithelial Cell Apoptosis ◽  
Ductal Elongation ◽  
Ductal Branching ◽  
Lobuloalveolar Development

We have previously demonstrated that overexpression of parathyroid hormone-related protein (PTHrP) in the mammary glands of transgenic mice results in defects in ductal elongation and branching during puberty and in lobuloalveolar development during pregnancy. In addition, we have shown that PTHrP is necessary for the formation of the initial ductal tree during embryonic mammary development. In order to examine the effect of varying the timing of PTHrP overexpression on mammary development, we created tetracycline-regulated, K14-tTA/Tet(O)-PTHrP double transgenic mice. In this report, we document that this 'tet-off' system directs transgene expression to the mammary gland and that it is fully repressed in the presence of tetracycline. Using these mice, we demonstrate that transient overexpression of PTHrP before birth causes defects in ductal branching during puberty and that overexpression of PTHrP during puberty decreases the rate of ductal elongation. Furthermore, we demonstrate that if PTHrP overexpression is initiated after ductal morphogenesis is completed, lobuloalveolar development is unaffected. Finally, we demonstrate that the impairment in ductal elongation caused by PTHrP is associated with an increase in the basal rate of epithelial cell apoptosis in terminal end buds and a failure to increase end bud cell proliferation and decrease apoptosis in response to estrogen and progesterone.

Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3539-3547 ◽  
Author(s):  
J.J. Wysolmerski ◽  
J.F. McCaughern-Carucci ◽  
A.G. Daifotis ◽  
A.E. Broadus ◽  
W.M. Philbrick
Keyword(s):  
Parathyroid Hormone ◽  
Transgenic Mice ◽  
Branching Morphogenesis ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Breast Development ◽  
Related Protein ◽  
Amino Terminal ◽  
Parathyroid Hormone Related Protein ◽  
Breast Hypoplasia

Parathyroid hormone-related protein (PTHrP) was originally discovered as the tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in many normal fetal tissues where it may participate in the regulation of organogenesis. In this report, we document that overexpression of PTHrP in myoepithelial cells in the mammary glands of transgenic mice resulted in a form of breast hypoplasia characterized by a profound defect in branching morphogenesis of the developing mammary duct system. In addition, transgenic mice manifested a defect in lobuloalveolar development during pregnancy that seemed to be, in part, the consequence of an impaired ability to form terminal ducts in response to estrogen and progesterone stimulation. The effects of PTHrP on branching morphogenesis during breast development appeared to be the result of amino-terminal PTH-like sequences that signal through the PTH/PTHrP receptor, since overexpression of parathyroid hormone itself in the mammary glands of transgenic mice caused a similar development phenotype, and delivery of PTHrP (1–36) via locally implanted slow-release pellets impaired breast development in normal mice. These results suggest that PTHrP, which is a native product of mammary epithelial and myoepithelial cells may participate in normal breast development, perhaps as a locally secreted growth inhibitor.

scholarly journals Progressive Pancreatic Islet Hyperplasia in the Islet-Targeted, Parathyroid Hormone-Related Protein-Overexpressing Mouse*

Endocrinology ◽  
1998 ◽  
Vol 139 (9) ◽  
pp. 3743-3751 ◽  
Author(s):  
Scott E. Porter ◽  
Robert L. Sorenson ◽  
Pamela Dann ◽  
Adolfo Garcia-Ocana ◽  
Andrew F. Stewart ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Pancreatic Islet ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Islet Hyperplasia
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