[Frontiers in Bioscience 2, a1-8, May 1, 1997]

	[Frontiers in Bioscience 2, a1-8, May 1, 1997] Reprints PubMed CAVEAT LECTOR
	THE CARBOXY-TERMINAL DOMAIN OF HUMAN SURFACTANT PROTEIN B IS NOT REQUIRED FOR SECRETION IN MILK OF TRANSGENIC MICE Sinai Yarus¹, Timothy E. Weaver², and Jeffrey M. Rosen¹ ¹ Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA ² Division of Neonatology and Pulmonary Biology, University of Cincinnati College of Medicine and Children's Hospital Medical Center, Cincinnati, Ohio 45267-0541, USA Received 3/24/97; Accepted 4/22/97; On-line 5/1/97 2. INTRODUCTION Previous attempts to produce recombinant hSP-B in the milk yielded only the proprotein (42 kDa) (1) suggesting that the mammary gland was unable to carry out the necessary post-translational proteolytic cleavage reactions required for the production of mature hSP-B. Analysis of SP-B expression in cell transfection experiments suggested that the amino-terminal domain of the proprotein is necessary for secretion, while the carboxy-terminal domain is not required (2). Therefore, we speculated that it might be possible to express a partially processed hSP-B protein in milk that could be used as a substrate for further in vitro processing to produce the mature hSP-B peptide. In order to test the feasibility of this approach, transgenic mice with a WAP/SP-BDELTA C transgene were generated. Use of the mammary gland as a bioreactor to produce heterologous proteins in milk is now well established (reviewed in (3-5)). In this study, the rat whey acidic protein (rWAP) promoter and 3' UTR sequences (6, 7) were employed to direct the expression of the SP-BDELTA C transgene to the murine mammary gland. These regulatory sequences have successfully directed the expression of several heterologous transgenes to the mammary gland (8, 9, 1).

[Frontiers in Bioscience 2, a1-8, May 1, 1997]
Reprints
PubMed
CAVEAT LECTOR

THE CARBOXY-TERMINAL DOMAIN OF HUMAN SURFACTANT PROTEIN B IS NOT REQUIRED FOR SECRETION IN MILK OF TRANSGENIC MICE

Sinai Yarus¹, Timothy E. Weaver², and Jeffrey M. Rosen¹

¹ Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA

² Division of Neonatology and Pulmonary Biology, University of Cincinnati College of Medicine and Children's Hospital Medical Center, Cincinnati, Ohio 45267-0541, USA

Received 3/24/97; Accepted 4/22/97; On-line 5/1/97

2. INTRODUCTION

Previous attempts to produce recombinant hSP-B in the milk yielded only the proprotein (42 kDa) (1) suggesting that the mammary gland was unable to carry out the necessary post-translational proteolytic cleavage reactions required for the production of mature hSP-B. Analysis of SP-B expression in cell transfection experiments suggested that the amino-terminal domain of the proprotein is necessary for secretion, while the carboxy-terminal domain is not required (2). Therefore, we speculated that it might be possible to express a partially processed hSP-B protein in milk that could be used as a substrate for further in vitro processing to produce the mature hSP-B peptide. In order to test the feasibility of this approach, transgenic mice with a WAP/SP-BDELTA C transgene were generated.

Use of the mammary gland as a bioreactor to produce heterologous proteins in milk is now well established (reviewed in (3-5)). In this study, the rat whey acidic protein (rWAP) promoter and 3' UTR sequences (6, 7) were employed to direct the expression of the SP-BDELTA C transgene to the murine mammary gland. These regulatory sequences have successfully directed the expression of several heterologous transgenes to the mammary gland (8, 9, 1).