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 |  |
Kidney diseases
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.
Cystic kidney
Based on the related genetic information, such as polycystic kidney disease (http://www.informatics.jax.org/mp/annotations/MP:0008528) and cystic kidney disease (http://www.informatics.jax.org/disease/DOID:2975) provided by The Jackson Laboratory, we generated knockout mice for genes associated with cystic kidney disease.
| Gene | Strain | Remarks |
|---|---|---|
| Anks6 | Anks6-KO | |
| Bicc1 | Bicc1-KO | |
| Muc1 | Muc1-KO | |
| Umod | Umod-KO | |
| Xylt2 | Xylt2-KO |
Lung diseases
Idiopathic pulmonary fibrosis
Based on the related genetic information of pulmonary fibrosis (http://www.informatics.jax.org/mp/annotations/MP:0006050) provided by The Jackson Laboratory, knockout mice were generated for genes associated with idiopathic pulmonary fibrosis (IPF), a type of idiopathic interstitial pneumonia (IDP).
| Gene | Strain | Remarks |
|---|---|---|
| Cav1 | Cav1-KO | |
| Cftr | Cftr-KO | |
| Cox4i2 | Cox4i2-KO | |
| Ctsk | Ctsk-KO | |
| Cxcr3 | Cxcr3-KO | No live mice was obtained due to lethality. |
| Cysltr2 | Cyltr2-KO | |
| Hck | Hck-KO | |
| Itga3 | Itga3-KO | |
| Sftpa1 | Sftpa1-KO | |
| Sftpc | Sftpc-KO | |
| Sftpd | Sftpd-KO | |
| Tnfrfs1a | Tnfrfs1a-KO | |
| Tnfrfs1b | Tnfrfs1b-KO | |
| Tomm5 | Tomm5 KO | |
| Trp53 | Trp53-KO | |
| Twsg1 | Twsg1-KO | No live mice was obtained due to lethality. |
| Wwtr1 | Wwtr1-KO | No 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 generated knockout mice (Eif2b1-KO and Mlc1-KO) of Eif2b1 and Mlc1 genes, respectively. In the future, we plan to generate knockout mice of other causative genes (Eif2b2, Eif2b3, Eif2b4, Eif2b5). Regarding Aars2 gene, flox mice (Aars2-flox) are now available.
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#5，Ace2-Tg#16，Ace2-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
- 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]