These SP-D knock-out mice exhibit progressive accumulation of lung surfactant lipids and proteins and are mildly obese. They are suitable for use in applications related to lung surfactant homeostasis, innate immunity and pulmonary inflammatory response.
Anne Marie Gillespie, University of California San Francisco
The Sftpd gene encodes for the C-type lectin glycoprotein surfactant protein D, which is secreted by pulmonary alveolar type II cells and nonciliated airway cells. The protein binds and coats bacteria and viruses to promote phagocytosis. These mice carry a knock-out mutation of the Sftpd gene in which exon 2, including the translation start site, has been replaced by a PGK-NEO cassette. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of lung tissue from homozygotes. Knock-mice mice exhibit progressive accumulation of surfactant lipids, surfactant protein A, and surfactant protein B in the alveolar space. By 8 weeks of age, the alveolar phospholipid pool was 8-fold higher than wildtype controls and a 10-fold increase in the number of alveolar macrophages is observed. Homozygotes are mildly obese and exhibit hyperphagia, elevated energy consumption, redistribution of fat deposits and insulin resistance. Knock-out mice have a 2 fold increase in basal levels of systemic gram negative bacterial endotoxin when compared to controls. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.
A targeting vector containing a PGK-NEO cassette was used to disrupt exon 2. The construct was electroporated into C57BL/6J x (Rb(11.16)2H x Rb(16.17)32Lub)F1 derived CB1-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into CD-1 blastocysts.
The resulting chimeric male animals were crossed to albino CD-1 female mice, and then backcrossed to C57BL/6 for at least 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Samuel Hawgood|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Sftpd-; SP-D-; Spd-|
|Gene Symbol and Name||Sftpd, surfactant associated protein D|
|Strain of Origin||C57BL/6J x (Rb(11.16)2H x Rb(16.17)32Lub)F1|
|Molecular Note||Replacement of exon 2 with a neomycin cassette.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the SP-D null mouse strain in a publication, please cite the originating article(s) and include JAX stock #027302 in your Materials and Methods section.