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 pro SP-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