Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Jeffrey Whitsett,   Children's Hospital Medical Center

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of lung tissue from homozygous mice. Homozygotes are more susceptible (pneumonia and sepsis) to group B streptococcal, P. aeruginosa, and H. influenzae infections due to impaired bacteria clearance. Alveolar macrophages have impaired superoxide radical production. Administration of surfactant protein A increases phagocytosis of bacteria by macrophages. When experimentally infected with respiratory syncytial virus or influenza A, homozygotes have increased viral titer, pulmonary inflammatory cell infiltration and cytokine levels. This mutant mouse strain represents a model that may be useful in studies of host defense against respiratory pathogens and innate immune function.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the 3' end of exon 3, intron 3 and the 5' end of exon 4. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to NIH Swiss black mice.

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Sftpa1^tm1Kor/Sftpa1^tm1Kor

        involves: 129P2/OlaHsd * NIH Black Swiss

• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:35250)
  • mice do not exhibit any altered lung inflammation
• increased susceptibility to bacterial infection (MGI Ref ID J:110382)
  • lung infiltrates are observed 6 hours after exposure to group B streptococcus (GBS) compared to in similarly treated wild-type mice that show infiltrate after 24 hours
  • at 48 hours post-infection with GBS, inflammation persists and is more severe than in similarly treated wild-type mice mice exhibit reduced bacterial clearance compared to wild-type mice
  • mice exhibit increased systemic infection with GBS compared to wild-type mice with increased splenic burden
  • GBS associated with alveolar macrophages is decreased compared to in wild-type mice
  • mice exhibit increased susceptibility to infection with Pneumocystis carinii compared to wild-type mice
• lung inflammation (MGI Ref ID J:110382)
  • lung infiltrates are observed 6 hours after exposure to group B streptococcus (GBS) compared to in similarly treated wild-type mice that show infiltrate after 24 hours
  • at 48 hours post-infection with GBS, inflammation persists and is more severe than in similarly treated wild-type mice
• respiratory system phenotype
• *normal* respiratory system phenotype (MGI Ref ID J:35250)
  • mice do not exhibit any altered lung structure, alveolar phospholipids pool size or composition, or lung inflammation
• abnormal surfactant physiology (MGI Ref ID J:111449)
  • surfactant exhibits decreased minimum surface tension and increased sensitivity to plasma inactivation compared to wild-type surfactant
  • mice exhibit fewer large aggregates of surfactant compared to in wild-type mice
  • the number of large surfactant aggregates following exposure to NMU (N-nitroso-N-methylurea) is decreased compared to in similarly treated wild-type mice
• lung inflammation (MGI Ref ID J:110382)
  • lung infiltrates are observed 6 hours after exposure to group B streptococcus (GBS) compared to in similarly treated wild-type mice that show infiltrate after 24 hours
  • at 48 hours post-infection with GBS, inflammation persists and is more severe than in similarly treated wild-type mice

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Sftpa1^tm1Kor/Sftpa1^tm1Kor

        involves: 129P2/OlaHsd

• respiratory system phenotype
• abnormal surfactant physiology (MGI Ref ID J:107841)
  • LPS-induced injury decreases surfactant clearance 40% compared to in similarly treated wild-type mice
• lung inflammation (MGI Ref ID J:107841)
  • LPS-induced injury increases the number of alveolar resident cells compared to in similarly treated wild-type mice
• homeostasis/metabolism phenotype
• abnormal phospholipid level (MGI Ref ID J:107841)
  • LPS-induced injury increases the level of phospholipids in lavage fluid 1.6-fold compared to in similarly treated wild-type mice
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:130958)
  • mice exhibit a normal inflammatory response following infection with Cryptococcus neoformans
• lung inflammation (MGI Ref ID J:107841)
  • LPS-induced injury increases the number of alveolar resident cells compared to in similarly treated wild-type mice

Sftpa1^tm1Kor/Sftpa1^tm1Kor

        involves: 129P2/OlaHsd * Black Swiss * C3H/HeN

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:130297)
  • all mice born in a corn dust environment (resulting in exposure to various bacteria) die within 48 hours
• immune system phenotype
• increased susceptibility to bacterial infection (MGI Ref ID J:130297)
  • mice born in a corn dust environment exhibit gastrointestinal abnormalities and high bacteria count in peritoneal fluid unlike wild-type mice
  • all mice born in a corn dust environment (resulting in exposure to various bacteria) die within 48 hours

Sftpa1^tm1Kor/Sftpa1^tm1Kor

        B6.129P2-Sftpa1^tm1Kor

• respiratory system phenotype
• abnormal surfactant physiology (MGI Ref ID J:130520)
  • following infection with mycoplasma, the numbers of large surfactant aggregates is decreased and higher protein to lipid ratios are present in the bronchoalveolar lavage fluid compared to similarly infected wild-type mice
• homeostasis/metabolism phenotype
• abnormal phospholipid level (MGI Ref ID J:130520)
  • mice exhibit a decrease in phospholipid content of the VLA (very large aggregates) fraction of the bronchalveolar lavage (BAL) fluid and an increase in the phospolipid levels of the ILA (intermediate large aggregates) fraction compared to in wild-type mice
  • however, the total phospolipid content of the BAL is normal

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Sftpa1^tm1Kor related

Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects

Internal/Organ Research
Lung Defects

Research Tools
Immunology and Inflammation Research (Macrophage Deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Sftpa1tm1Kor
Allele Name		targeted mutation 1, Thomas R Korfhagen
Allele Type		Targeted (knock-out)
Common Name(s)		SP-A(-);
Mutation Made By		Jeffrey Whitsett,   Children's Hospital Medical Center
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Sftpa1, surfactant associated protein A1
Chromosome		14
Gene Common Name(s)		AC068139.6; MGC105453; MGC133365; PSAP; PSPA; SFTP1; SP-A; Sftp-1; Sftp1; Sftpa; Sftpl; surfactant pulmonary associated protein A1; surfactant-associated protein 1;
Molecular Note		Portions of exons 3 and 4 (base pairs 795 through 1049) were deleted by the insertion of a PGK-neo cassette. Northern blot analysis of RNA obtained from lung tissue showed an absence of transcript in homozygous mutant mice. The lack of encoded protein was confirmed by Western blot analysis of lung homogenates and immunohistochemical staining of alveolar type II cells. [MGI Ref ID J:35250]

Genotyping

Genotyping Information

Genotyping Protocols

Sftpa^tm1Kor, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Korfhagen TR; Bruno MD; Ross GF; Huelsman KM; Ikegami M; Jobe AH; Wert SE; Stripp BR; Morris RE; Glasser SW; Bachurski CJ; Iwamoto HS; Whitsett JA. 1996. Altered surfactant function and structure in SP-A gene targeted mice. Proc Natl Acad Sci U S A 93(18):9594-9. [PubMed: 8790375]  [MGI Ref ID J:35250]

Additional References

LeVine AM; Bruno MD; Huelsman KM; Ross GF; Whitsett JA; Korfhagen TR. 1997. Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 158(9):4336-40. [PubMed: 9126996]  [MGI Ref ID J:110382]

LeVine AM; Gwozdz J; Stark J; Bruno M; Whitsett J; Korfhagen T. 1999. Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. J Clin Invest 103(7):1015-21. [PubMed: 10194474]  [MGI Ref ID J:110384]

LeVine AM; Kurak KE; Bruno MD; Stark JM; Whitsett JA; Korfhagen TR. 1998. Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol 19(4):700-8. [PubMed: 9761768]  [MGI Ref ID J:110383]

LeVine AM; Kurak KE; Wright JR; Watford WT; Bruno MD; Ross GF; Whitsett JA; Korfhagen TR. 1999. Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice. Am J Respir Cell Mol Biol 20(2):279-86. [PubMed: 9922219]  [MGI Ref ID J:110385]

LeVine AM; Whitsett JA; Gwozdz JA; Richardson TR; Fisher JH; Burhans MS; Korfhagen TR. 2000. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 165(7):3934-40. [PubMed: 11034401]  [MGI Ref ID J:110381]

Sftpa1^tm1Kor related

Borron P; McIntosh JC; Korfhagen TR; Whitsett JA; Taylor J; Wright JR. 2000. Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo. Am J Physiol Lung Cell Mol Physiol 278(4):L840-7. [PubMed: 10749762]  [MGI Ref ID J:62405]

George CL; Goss KL; Meyerholz DK; Lamb FS; Snyder JM. 2008. Surfactant-associated protein A provides critical immunoprotection in neonatal mice. Infect Immun 76(1):380-90. [PubMed: 17967856]  [MGI Ref ID J:130297]

Giles SS; Zaas AK; Reidy MF; Perfect JR; Wright JR. 2007. Cryptococcus neoformans Is Resistant to Surfactant Protein A Mediated Host Defense Mechanisms. PLoS ONE 2(12):e1370. [PubMed: 18159253]  [MGI Ref ID J:130958]

Hickman-Davis JM; Gibbs-Erwin J; Lindsey JR; Matalon S. 2004. Role of surfactant protein-A in nitric oxide production and mycoplasma killing in congenic C57BL/6 mice. Am J Respir Cell Mol Biol 30(3):319-25. [PubMed: 12959946]  [MGI Ref ID J:97300]

Hickman-Davis JM; Wang Z; Fierro-Perez GA; Chess PR; Page GP; Matalon S; Notter RH. 2007. Surfactant dysfunction in SP-A-/- and iNOS-/- mice with mycoplasma infection. Am J Respir Cell Mol Biol 36(1):103-13. [PubMed: 16917077]  [MGI Ref ID J:130520]

Ikegami M; Korfhagen TR; Whitsett JA; Bruno MD; Wert SE; Wada K; Jobe AH. 1998. Characteristics of surfactant from SP-A-deficient mice. Am J Physiol 275(2 Pt 1):L247-54. [PubMed: 9700084]  [MGI Ref ID J:111449]

Korfhagen TR; LeVine AM; Whitsett JA. 1998. Surfactant protein A (SP-A) gene targeted mice. Biochim Biophys Acta 1408(2-3):296-302. [PubMed: 9813377]  [MGI Ref ID J:51270]

Kuzmenko AI; Wu H; Wan S; McCormack FX. 2005. Surfactant protein A is a principal and oxidation-sensitive microbial permeabilizing factor in the alveolar lining fluid. J Biol Chem 280(27):25913-9. [PubMed: 15890661]  [MGI Ref ID J:109974]

LeVine AM; Bruno MD; Huelsman KM; Ross GF; Whitsett JA; Korfhagen TR. 1997. Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 158(9):4336-40. [PubMed: 9126996]  [MGI Ref ID J:110382]

LeVine AM; Hartshorn K; Elliott J; Whitsett J; Korfhagen T. 2002. Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection. Am J Physiol Lung Cell Mol Physiol 282(3):L563-72. [PubMed: 11839553]  [MGI Ref ID J:75614]

LeVine AM; Kurak KE; Wright JR; Watford WT; Bruno MD; Ross GF; Whitsett JA; Korfhagen TR. 1999. Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice. Am J Respir Cell Mol Biol 20(2):279-86. [PubMed: 9922219]  [MGI Ref ID J:110385]

Linke MJ; Harris CE; Korfhagen TR; McCormack FX; Ashbaugh AD; Steele P; Whitsett JA; Walzer PD. 2001. Immunosuppressed surfactant protein A-deficient mice have increased susceptibility to Pneumocystis carinii infection. J Infect Dis 183(6):943-52. [PubMed: 11237812]  [MGI Ref ID J:120552]

McCormack FX; Gibbons R; Ward SR; Kuzmenko A; Wu H; Deepe GS Jr. 2003. Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem 278(38):36250-6. [PubMed: 12857753]  [MGI Ref ID J:85539]

Quintero OA; Korfhagen TR; Wright JR. 2002. Surfactant protein A regulates surfactant phospholipid clearance after LPS-induced injury in vivo. Am J Physiol Lung Cell Mol Physiol 283(1):L76-85. [PubMed: 12060563]  [MGI Ref ID J:107841]

Vandivier RW; Ogden CA; Fadok VA; Hoffmann PR; Brown KK; Botto M; Walport MJ; Fisher JH; Henson PM; Greene KE. 2002. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol 169(7):3978-86. [PubMed: 12244199]  [MGI Ref ID J:120404]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a mixed 129P2, NIH Swiss black background, andmay be maintained as a homozygote on the same. SPF (specific pathogen free) conditions required.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.