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Strain Name:
FVB/NTac-Ism1em1Nusrg/Mmucd
Stock Number:
076032-UCD
Citation ID:
RRID:MMRRC_076032-UCD
Other Names:
FVB-NtacIsm1tmΔ59Nusrg, Ism1-/-

Strain Information

QUALITY CONTROL OF FVB/NTac-Ism1em1Nusrg/Mmucd  |  University of California at Davis
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3YES
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status YES
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3 n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distributionn.d.
Fecundity/breeding performancen.d.

1 When indicated as "assessed by MMRRC" ("YES"), please note that the information presented on this strain is to the best of our knowledge correct and up-to-date at the the MMRRC Distribution Center assigned to maintain and distribute this strain. This information is subject to change due to breeding, maintenance, and other actions. Please direct any questions on the information presented in this table to the MMRRC Distribution Center.

2 If an assessment has not been performed by the MMRRC (as indicated by "NO"), investigators may request specific testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Ism1em1Nusrg
Name: isthmin 1, angiogenesis inhibitor; endonuclease-mediated mutation 1, Ruowen Ge
Synonyms: Ism1tm59Nusrg, Ism1em1Fgnx
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 2
Alteration at locus: CRISPR
Ism1
Name: isthmin 1, angiogenesis inhibitor
Synonyms: 5430433G21Rik
Type: Gene
Species: Mouse
Chromosome: 2
NCBI: 319909
Homologene: 19061
Genetic Alterations
A 59 bp deletion in exon 1 of the Ism1 gene was generated using CRISPR-Cas9 genome editing. This deletion causes an out-of-frame mutation that results in a disruption of the ISM1 protein and complete loss of functional (whole body knockout) ISM1 expression throughout the body.
ES Cell Line
Not applicable
Phenotype
Ism1 knockout (Ism1-/-) mice are viable, developmentally normal, fertile, and exhibit no gross behavioral abnormalities.

Histopathological examination reveals spontaneous and progressive emphysema in Ism1-/- mice, with a more pronounced phenotype in the FVB/NTac background compared to C57BL/6J. The emphysema phenotype becomes evident by 8 weeks of age. Heterozygous (Ism1+/-) mice exhibit intermediate ISM1 expression and a milder emphysema phenotype, indicating haploinsufficiency.

Ism1-/- lungs display deterioration of the alveolar extracellular matrix, including elastin fiber loss and septal rupture, as demonstrated by fluorescent collagen/elastin labeling and Verhoeff–Van Gieson staining. Increased alveolar macrophage accumulation, elevated MMP-12 and MMP-9 expression, chronic inflammation, and mucus hypersecretion are observed.

Pulmonary function testing at 2 months shows increased total lung capacity, elevated residual volume, increased static and dynamic compliance, reduced FEV100, and increased airway resistance, consistent with hyperinflation and airflow obstruction seen in human chronic obstructive pulmonary disease (COPD). No gross histological abnormalities are observed in other major organs, including the brain, at 2 months of age.

This strain is a useful model for studying COPD, emphysema, and bronchitis.
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Apoptosis
  • Cancer
  • Cell Biology
  • Immunology and Inflammation
  • Models for Human Disease
Submitter
Ruowen Ge, Ph.D., National University of Singapore.
Primary Reference

Lam TYW, Nguyen N, Peh HY, Shanmugasundaram M, Chandna R, Tee JH, Ong CB, Hossain MZ, Venugopal S, Zhang T, Xu S, Qiu T, Kong WT, Chakarov S, Srivastava S, Liao W, Kim JS, Teh M, Ginhoux F, Fred Wong WS, Ge R. ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2019161119. doi: 10.1073/pnas.2019161119. (Medline PMCID: 8794848)

Nguyen N, Xu S, Lam TYW, Liao W, Wong WSF, Ge R. ISM1 suppresses LPS-induced acute lung injury and post-injury lung fibrosis in mice. Mol Med. 2022 Jun 25;28(1):72. doi: 10.1186/s10020-022-00500-w. (Medline PMCID: 9233842)

Strain Development
Ism1 knockout mice were generated via CRISPR/ Cas9-mediated genome editing on two backgrounds, FVB/NTac and C57BL/6J mice. This strain (RRID:MMRRC_076032-UCD) was developed on the FVB/NTac background.

Briefly, CRISPR guides and Cas9 protein were microinjected into FVB/Ntac zygotes, and founder mice were identified by PCR and sequencing. Founders were bred to FVB/Ntac to establish the line through N1 and N2 generations. Heterozygous N2 mice were intercrossed to generate homozygous mutant for phenotyping. N3 homozygous mutant mice were mated to obtain more homozygous mutant mice. Prior to being accepted into the MMRRC, the line was maintained by periodic outcrossing of homozygous mice to FVB/Ntac mice every 6-12 months to produce heterozygous mice for colony maintenance.

Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain's tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.
Coat Color
White
Eye
Pink
MMRRC Breeding System
Random intra-strain mating
Generation
N/A
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
7 to 9

Order Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Acting Lead, TTI, NUS Enterprise .

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Acting Lead, TTI, NUS Enterprise

- Products for this strain are Not Yet Available for Ordering
- If you register interest in this strain, you will be notified when it becomes available for ordering.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.