SP-A KO hTG SP-A1 mice express human SFTPA1 (surfactant associated protein A1 or SP-A1) variant 6A4 under the control of the human SFPTC promoter on a Sftpa1 null background. This strain may be useful for studying lung function, surfactant structure, host defense and inflammation.

Not applicable

SFTPA1 (surfactant associated protein A1 or SP-A1), SFTPA2 (surfactant associated protein A2 or SP-A2), and a pseudogene encode SP-A, a C-type lectin called collectin. Each SFTPA gene has several genetic variants found in the 3’ UTR and is responsible for differential binding of miRNA. SP-A1 is expressed in alveolar epithelial type II cells; SP-A2 is expressed in tracheal and bronchial submucosal gland cells in the lung. Rodents have only one SFTPA gene, Sftpa1. SP-A is involved in in surfactant homeostasis and in the defense against respiratory pathogens. It is also a modulator of lung function, surfactant structure, host defense and inflammation.

SP-A KO hTG SP-A1(6A4) mice constitutively express human SFTPA1 (variant 6A4) under the control of the human SFPTC promoter on a Sftpa1 null background. Variant 6A4 (GenBank HQ021436.1) may be associated with lung carcinoma and idiopathic pulmonary fibrosis. Mice homozygous for the KO and hemizygous for the transgene are viable and fertile. The donating investigator has not attempted to generate mice homozygous for the transgene. SP-A KO hTG SP-A1(6A4) mice lack tubular myelin as assessed by electron microscopy and have a distinctive response to various insults such as ozone exposure and/or infection as compared to other SP-A mouse strains.

Of note, the following SP-A mutants are distributed:
Mice expressing human SFTPA1 variants 6A2 (MMRRC Stock No. 69751) and 6A4 (MMRRC Stock No. 69748) .
Mice expressing human SFTPA2 variants 1A3 (MMRRC Stock No. 69749) and 1A0 (MMRRC Stock No. 69750).
Mice with the SP-A KO are distributed as MMRRC Stock No. 69752.

The hTG SP-A1(6A4) transgenic construct contains the 3.7 kb human SFTPC (surfactant associated protein C) promoter, the 1.3 kb human SFTPA1 (surfactant associated protein A1) variant 6A4 coding sequence containing the 5’ and 3’ UTR and the entire coding region followed by an SV40 polyA signal. The linearized construct was microinjected into the pronuclei of fertilized C57BL/6 mice. Founder line T2 exhibits higher protein expression than the other founder lines.

The Sftpa1^tm1Haw allele was created by Dr. Samuel Hawgood (University of California, San Francisco). The SP-A (Sftpa1^tm1Haw) targeting vector was designed to replace exons 2, 3, and 4 including the translation start site of the Sftpa1 (surfactant associated protein A1) gene on chromosome 14 with a neomycin cassette. The construct was electroporated into (C57BL/6 x 129/Sv)F1-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred with CD-1 females.

hTG SP-A1(6A4) mice were crossed to SP-A KO mice on a mixed background. Mice are hemizygous for the transgene and homozygous for the KO allele. Sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

SP-A KO (mice not expressing SP-A)

The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

Joanna Floros, Ph.D., Penn State University, College of Medicine.