title: Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia.
abstract: Surfactant protein B (SP-B) is essential for lung function. Previous studies have indicated that a SP-B 1580C/T polymorphism (SNP rs1130866) was associated with lung diseases including pneumonia. The SNP causes an altered N-linked glycosylation modification at Asn129 of proSP-B, e.g. the C allele with this glycosylation site but not in the T allele. This study aimed to generate humanized SP-B transgenic mice carrying either SP-B C or T allele without a mouse SP-B background and then examine functional susceptibility to bacterial pneumonia in vivo. A total of 18 transgenic mouse founders were generated by the DNA microinjection method. These founders were back-crossed with SP-B KO mice to eliminate mouse SP-B background. Four founder lines expressing similar SP-B levels to human lung were chosen for further investigation. After intratracheal infection with 50 μl of Pseudomonas aeruginosa solution (1 × 10(6) CFU/mouse) or saline in SP-B-C, SP-B-T mice the mice were sacrificed 24 h post-infection and tissues were harvested. Analysis of surfactant activity revealed differential susceptibility between SP-B-C and SP-B-T mice to bacterial infection, e.g. higher minimum surface tension in infected SP-B-C versus infected SP-B-T mice. These results demonstrate for the first time that human SP-B C allele is more susceptible to bacterial pneumonia than SP-B T allele in vivo.
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.
authors.forename: Rimei
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.
authors.forename: Yi Y
authors.initials: YY
authors.lastname: Zuo
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cooney
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. Electronic address: wangg@upstate.edu.
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000378:metabolism / Q000382:microbiology; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics* / Q000378:metabolism*
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B
keywords: Allele; Humanized transgenic mice; Pneumonia; Psedomonas aeruginosa; Surface tension; Surfactant protein B