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Am. J. Respir. Cell Mol. Biol., Volume 20, Number 5, May, 1999 953-963

Genomic Organization of the Mouse Gene for Lung Surfactant Protein D

Peter R. Lawson, Vivienne C. Perkins, Uffe Holmskov, and Kenneth B. M. Reid

MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, Oxford, United Kingdom; and Department of Medical Microbiology, Institute of Medical Biology, University of Odense, Odense, Denmark

Lung surfactant protein (SP)-D belongs to the family of soluble collagenous C-type lectins, named collectins. SP-D participates in the local innate immune defense of the lung, eliciting various effector functions by acting as a pattern recognition receptor for the carbohydrate structures on inhaled microorganisms and particulate matter. This work describes the isolation and characterization of the mouse SP-D gene (Sftpd), which spans 8 exons over 14 kb of sequence and shows an overall organization similar to other collectin genes. The complete 5' untranslated region of the messenger RNA, absent from the published complementary DNA for mouse SP-D, was also cloned and is shown to be encoded by a single exon. Analysis of 3.5 kb of 5' flanking nucleotide sequence for Sftpd is described and reveals positional conservation of a number of transcription factor binding sites on comparison of Sftpd with the human SP-D gene and the bovine conglutinin gene. In addition, a single copy SP-D-like gene has been shown to be present in mammals, birds, and amphibians but is absent in fish. An atypical, rodent-specific, long terminal repeat of retroviral origin containing a minisatellite that has become inserted in Sftpd is described. Three new polymorphic microsatellites are also described, one of which is just 160 base pairs upstream of Sftpd. This microsatellite was used to map the gene to the central region of chromosome 14; fine-scale mapping indicates that it lies in a 5.64-centimorgan area between D14Mit45 and D14Mit60. This will allow the easy identification of the collectin gene cluster and aid in the construction of a physical map over this region.




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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1999 American Thoracic Society.