Genomic Organization of the Mouse Gene for Lung Surfactant Protein D

Abstract

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.

Porcine Lung Surfactant Protein D: Complementary DNA Cloning, Chromosomal Localization, and Tissue Distribution

“…The 177-aa long collagen-like region is of the same length of that seen in humans and rodents, in contrast to bovine SP-D, for which the collagen-like region is 6 aa shorter. The porcine SP-D gene probably has a similar genomic organization across the collagen-like encoding region as seen in the human and murine genes (37,38), which are composed of four exons each of 117 bp. Indeed, the position of one of the predicted introns has been confirmed by genomic PCR sequencing (Fig.…”

“…The PCR products amplified from this genomic DNA region and the plasmid clone gave the same expected size PCR product of 381 bp. For the collagen region variation, the extra cysteine is in the first collagen-encoding exon close to the intronexon boundary predicted from the human and mouse genes (37,38). The extra cysteine was examined by amplifying the first two collagen-encoding exons, including the predicted short intervening intron.…”

Surfactant Protein D Facilitates Cryptococcus neoformans Infection

“…Such studies might consider whether the various SP-D polymorphisms described in the literature (24,32,33,35,54) affect susceptibility to C. neoformans infection and/or C. gattii infection and, if so, whether genetic screening may facilitate infection risk stratification for prevention in individuals possessing other risk factors for cryptococcal disease. The present study provides evidence that SP-D is subverted by C. neoformans cells for increased uptake by immune cells and protection against oxidative stress, thus aiding disease progression.…”

Evolution of collagens

“…The second group includes collagen genes composed of only phase 1 exons. This group contains all of the defense collagen genes, as well as type XVII collagen and EMILIN genes (Gatalica et al, 1997;Lawson et al, 1999;Doliana et al, 2000). The third group is composed mainly of phase 0 exons, which is represented by the genes encoding types XV and XVIII collagens.…”