RGD Reference Report - Creation of X-linked Alport syndrome rat model with Col4a5 deficiency. - Rat Genome Database

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Creation of X-linked Alport syndrome rat model with Col4a5 deficiency.

Authors: Namba, Masumi  Kobayashi, Tomoe  Kohno, Mayumi  Koyano, Takayuki  Hirose, Takuo  Fukushima, Masaki  Matsuyama, Makoto 
Citation: Namba M, etal., Sci Rep. 2021 Oct 21;11(1):20836. doi: 10.1038/s41598-021-00354-y.
RGD ID: 329845598
Pubmed: PMID:34675305   (View Abstract at PubMed)
PMCID: PMC8531394   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-021-00354-y   (Journal Full-text)

Alport syndrome is an inherited chronic human kidney disease, characterized by glomerular basement membrane abnormalities. This disease is caused by mutations in COL4A3, COL4A4, or COL4A5 gene. The knockout mice for Col4α3, Col4α4, and Col4α5 are developed and well characterized for the study of Alport syndrome. However, disease progression and effects of pharmacological therapy depend on the genetic variability. This model was reliable only to mouse. In this study, we created a novel Alport syndrome rat model utilizing the rGONAD technology, which generated rat with a deletion of the Col4α5 gene. Col4α5 deficient rats showed hematuria, proteinuria, high levels of BUN, Cre, and then died at 18 to 28¬†weeks of age (Hemizygous mutant males). Histological and ultrastructural analyses displayed the abnormalities including parietal cell hyperplasia, mesangial sclerosis, and interstitial fibrosis. Then, we demonstrated that α3/α4/α5 (IV) and α5/α5/α6 (IV) chains of type IV collagen disrupted in Col4α5 deficient rats. Thus, Col4α5 mutant rat is a reliable candidate for the Alport syndrome model for underlying the mechanism of kidney diseases and further identifying potential therapeutic targets for human renal diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Col4a5  (collagen type IV alpha 5 chain)
Col4a5em1Matsu  (collagen type IV alpha 5 chain; CRISPR/Cas9 induced mutant 1, Matsu)
Col4a5em2Matsu  (collagen type IV alpha 5 chain; CRISPR/Cas9 induced mutant 2, Matsu)
Col4a5em3Matsu  (collagen type IV alpha 5 chain; CRISPR/Cas9 induced mutant 3, Matsu)

Genes (Mus musculus)
Col4a5  (collagen, type IV, alpha 5)

Genes (Homo sapiens)
COL4A5  (collagen type IV alpha 5 chain)


Additional Information