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Mouse model library for rare diseases

A project to comprehensively generate knockout (KO) mice of rare disease-related genes using genome editing technology was initiated in FY 2018. Relatedly, we are also creating mice that can be used as research tools for rare diseases. The mouse strains will be sequentially distributed through the Experimental Animal Research Resource Bank as soon as the resource preparation (creation and quality evaluation of frozen embryos and/or sperm) are completed. A strain with a link to the strain’s web-page is already available.

If you have any questions or comments about this project, please contact us at Contact us.

Hermansky-Pudlak syndrome

KO mice were generated for nine causative genes of Hermansky-Pudlak syndrome (HPS), one type of ocular cutaneous leukoderma. Some of the causative genes are involved in gastrointestinal abnormalities (similar to Crohn's disease) and interstitial pneumonia. Therefore, these mice are expected to be used as symptom models not only for HPS but also for various diseases.

Gene Strain Coat color
Hps1 Hps1-KO
Ap3B1 (Hps2) Ap3B1-KO
Hps3 Hps3-KO
Hps4 Hps4-KO
Hps5 Hps5-KO
Hps6 Hps6-KO
Dtnbp1 Dtnbp1-KO
Bloc1s3 Bloc1s3-KO
Bloc1s6 Bloc1s6-KO
Wild-type C57BL/6N

Alport syndrome

Mice (Col4a4-KO) deficient for Col4a4, one of the genes responsible for Alport syndrome, which presents with chronic nephritis, hearing loss, and ocular complications, were generated.

Idiopathic pulmonary fibrosis

Based on the related genetic information of pulmonary fibrosis (http://www.informatics.jax.org/mp/annotations/MP:0006050) provided by Jackson Laboratory, knockout mice were generated for genes associated with idiopathic pulmonary fibrosis (IPF), a type of idiopathic interstitial pneumonia (IDP)

GeneStrainRemarks
Cav1Cav1-KO
CftrCftr-KO
Cox4i2Cox4i2-KO
CtskCstk-KO
Cxcr3Cxcr3-KONo live mice was obtained due to lethality.
Cysltr2Cyltr2-KO
HckHck-KO
Itga3Itga3-KO
Sftpa1Sftpa1-KO
SftpcSftpc-KO
SftpdSftpd-KO
Tnfrfs1aTnfrfs1a-KO
Tnfrfs1bTnfrfs1b-KO
Tomm5Tomm5-KO
Trp53Trp53-KO
Twsg1Twsg1-KONo live mice was obtained due to lethality.
Wwtr1Wwtr1-KONo live mice was obtained due to lethality.

Neuromuscular diseases

Canavan disease

We have developed knockout mice (Aspa-KO) of the Aspa gene, which is the causative gene of Canavan disease.

Progressive leukoencephalopathy

Among the causative genes of progressive leukoencephalopathy, we first generated knockout mice (Eif2b1-KO) of the Eif2b1 gene. In the future, we plan to generate knockout mice of other causative genes (Mlc1, Eif2b2, Eif2b3, Eif2b4, Eif2b5, Aars2).

Mice as tools for rare disease research

Hairless 4C30 mice

Hairless mice (Hairless 4C30) were generated by knocking out the hairless gene (Hr) in 4C30 mice, a model of dilated cardiomyopathy.

Mup-KO mice

In mice, a large amount of major urinary protein (MUP) produced by the liver is excreted in the urine, so that even health mice show proteinuria. However, the gene is not expressed in humans. Therefore, mice (Mup-KO) knocked out of the Mup gene cluster by genome editing (CRISPR/Cas9) were generated.

Mice as research tools for new coronavirus infections

Ace2-KO mice

We have developed knockout mice (Ace2-KO) of the Ace2 gene. It is possible to cross human Ace2-Tg mice (Ace2-Tg#5Ace2-Tg#16Ace2-Tg#17) with the Ace2-KO mice to produce mice whose Ace2 molecules are humans only.

Dpp4-KO mice

We have developed knockout mice (Dpp4-KO) of the Dpp4 gene and are currently developing them as resources. It is possible to cross human Dpp4-Tg mice with the Dpp4-KO mice to produce mice whose Dpp4 molecules are humans only.

Mice as research tools for cellular immunity

We have created knockout mice of Fc receptors as tools for the analysis of cellular immunity.

Fcgr1-KO

Knockout mice (Fcgr1-KO) for Fcgr1 gene.

Fcgr2,3,4-triple KO

Since three genes, Fcgr2b (reverse strand), Fcgr4 (forward strand), and Fcgr3 (reverse strand), located in the same order on chromosome 1, we created mice in which all three genes were simultaneously knocked out by deleting the genome sequence between the 3'-UTR of Fcgr2 and the 5'-UTR of Fcgr3 by genome editing. Please refer to the strain description of Fcgr234-KO mice for details.

Fcer1g-KO

Knockout mice for Fcer1g gene (under development as resources).

References

  1. Suzuki O, Koura M, Uchio-Yamada K, and Sasaki M. (2021) Urinary protein analysis in mice lacking major urinary proteins. Exp Anim 70(3):406-411. [PMID:33883349]