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Developmental regulation of the ovine β‐lactoglobulin/human serum albumin transgene is distinct from that of the β‐lactoglobulin and the endogenous β‐casein genes in the mammary gland of transgenic mice
Year:
1995
Source of publication :
Developmental Genetics
Authors :
Barash, Itamar
;
.
Baruch, Ariela
;
.
Shani, Moshe
;
.
Volume :
16
Co-Authors:
Baruch, A., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Shani, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Hurwitz, D.R., Rhône Poulenc Rorer Central Research, Collegeville, Pennsylvania, United States, ALG, 734 Forest Street, Marlboro, Massachusetts, 01752, United States
Barash, I., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Facilitators :
From page:
241
To page:
252
(
Total pages:
12
)
Abstract:
We compared the developmental pattern of expression of the sheep β‐lactoglobulin (BLG), the chimeric BLG/human serum albumin (HSA), and the endogenous murine β‐casein genes in the mammary gland of virgin, pregnant and lactating transgenic mice, both at the RNA (expression) and protein (synthesis and secretion) levels. The BLG and casein genes were expressed at very low levels in virgin animals and during early stages of pregnancy. The increase in the expression of these genes started at the second half of pregnancy and reached a peak between the end of pregnancy and day 10 of lactation. The accumulation of their RNA coincided with that of the corresponding proteins, indicating a transcriptional control of expression of these genes. The expression and secretion patterns of the endogenous casein gene in transgenic and nontransgenic mice were indistinguishable. The hybrid BLG/HSA gene constructs displayed distinct patterns of expression in virgin animals and at early stage of pregnancy, from that of the BLG transgene or the endogenous mouse milk protein gene. High levels of expression (17–60% of that on day 18 of pregnancy) were detected in the mammary gland of virgin animals. At day 5 of pregnancy there was a dramatic decrease in HSA synthesis and secretion in all transgenic strains tested. The down‐regulation, revealed by immunoprecipitation and immunohistochemical studies, demonstrated that at that stage of pregnancy only 10–18% of ductal structures contained HSA expressing cells in contrast to the majority of ducts expressing HSA in virgin animals. These morphological studies also demonstrated that the down‐regulation in HSA synthesis and secretion was correlated with the transition from ducts comprised of a single layer of epithelial cells (characteristic of the virgin state) to ducts composed of multilayers of such cells. In two of the three transgenic strains tested, the down‐regulation at the protein level was associated with a similar decrease in HSA transcripts. In the exceptional strain no. 23, HSA transcripts continued accumulating even at this stage. The differences in the control of expression at the RNA level between these transgenic strains were also confirmed by in situ hybridization. Our results suggest the involvement of at least two regulatory mechanisms effective at early stages of gestation in the control of expression/secretion of the HSA transgene targeted for expression in the mammary gland by the BLG milk protein promoter. These putative mechanisms may play key roles in the interplay between normal mammogenesis and lactogenesis. Thus, transgenic mice expressing BLG/HSA gene constructs at early stages of gestation would be valuable in further dissecting these mechanisms. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc.
Note:
Related Files :
Animal
animal experiment
beta casein
Female
lactation
mice
pregnancy
sheep
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Related Content
More details
DOI :
10.1002/dvg.1020160304
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
21810
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:47
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Scientific Publication
Developmental regulation of the ovine β‐lactoglobulin/human serum albumin transgene is distinct from that of the β‐lactoglobulin and the endogenous β‐casein genes in the mammary gland of transgenic mice
16
Baruch, A., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Shani, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Hurwitz, D.R., Rhône Poulenc Rorer Central Research, Collegeville, Pennsylvania, United States, ALG, 734 Forest Street, Marlboro, Massachusetts, 01752, United States
Barash, I., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Developmental regulation of the ovine β‐lactoglobulin/human serum albumin transgene is distinct from that of the β‐lactoglobulin and the endogenous β‐casein genes in the mammary gland of transgenic mice
We compared the developmental pattern of expression of the sheep β‐lactoglobulin (BLG), the chimeric BLG/human serum albumin (HSA), and the endogenous murine β‐casein genes in the mammary gland of virgin, pregnant and lactating transgenic mice, both at the RNA (expression) and protein (synthesis and secretion) levels. The BLG and casein genes were expressed at very low levels in virgin animals and during early stages of pregnancy. The increase in the expression of these genes started at the second half of pregnancy and reached a peak between the end of pregnancy and day 10 of lactation. The accumulation of their RNA coincided with that of the corresponding proteins, indicating a transcriptional control of expression of these genes. The expression and secretion patterns of the endogenous casein gene in transgenic and nontransgenic mice were indistinguishable. The hybrid BLG/HSA gene constructs displayed distinct patterns of expression in virgin animals and at early stage of pregnancy, from that of the BLG transgene or the endogenous mouse milk protein gene. High levels of expression (17–60% of that on day 18 of pregnancy) were detected in the mammary gland of virgin animals. At day 5 of pregnancy there was a dramatic decrease in HSA synthesis and secretion in all transgenic strains tested. The down‐regulation, revealed by immunoprecipitation and immunohistochemical studies, demonstrated that at that stage of pregnancy only 10–18% of ductal structures contained HSA expressing cells in contrast to the majority of ducts expressing HSA in virgin animals. These morphological studies also demonstrated that the down‐regulation in HSA synthesis and secretion was correlated with the transition from ducts comprised of a single layer of epithelial cells (characteristic of the virgin state) to ducts composed of multilayers of such cells. In two of the three transgenic strains tested, the down‐regulation at the protein level was associated with a similar decrease in HSA transcripts. In the exceptional strain no. 23, HSA transcripts continued accumulating even at this stage. The differences in the control of expression at the RNA level between these transgenic strains were also confirmed by in situ hybridization. Our results suggest the involvement of at least two regulatory mechanisms effective at early stages of gestation in the control of expression/secretion of the HSA transgene targeted for expression in the mammary gland by the BLG milk protein promoter. These putative mechanisms may play key roles in the interplay between normal mammogenesis and lactogenesis. Thus, transgenic mice expressing BLG/HSA gene constructs at early stages of gestation would be valuable in further dissecting these mechanisms. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc.
Scientific Publication
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