The COL4A3 gene encodes alpha 3 chain of type IV collagen, which is a key component of the glomerular basement membrane (GBM) and is also the target of pathogenic autoantibodies in human Goodpasture disease (so these are Goodpasture autoantigen-humanized mice). The α3(IV) chain forms α3α4α5(IV) heterotrimers which are secreted and incorporated into the GBM. Mutations in the COL4A3, COL4A4 or COL4A5 genes that prevent the assembly of α3α4α5(IV) heterodimers cause Alport syndrome. Mice expressing a human COL4A3/COL4A4 YAC transgene ("Tg") mouse line was mated to COL4A3-/- mice ("KO" mice) and maintained as a Tg/KO line.

Record History
Added on May 19, 2020 at 11:18 AM by Skelton, Jennifer
Modified on May 19, 2020 at 11:43 AM by Skelton, Jennifer
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VCMR: Vanderbilt Cryopreserved Mouse Repository Master
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Mouse Information

Common Name COL4A3/COL4A4-Tg
Date Cryopreserved 2013-10-01
Method of Cryopreservation Sperm
Trial IVF % Fertilization 79.00%

Genetic Alterations

Mutation #1: BAC or Transgene Insertion
BAC Clone Number AB1380
BAC Resource Library CEH-YAC
Expressed Gene Name: COL4A3/COL4A4
MGI: Tg(COL4A3/Col4A4)1Lahe
Zygosity at cryopreservation Homozygous
PCR Genotyping Protocol Not provided
A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice. (2003) Am J Pathol 163: 1633-44 (Added 12/10/2013)
PMID: 14507670
Mutation #2: Targeted Mutagenesis
Allele Name: collagen, type IV, alpha 3; targeted mutation 1, Jeffrey H Miner
Symbol: Col4a3tm1Jhm
MGI: 1934893
Zygosity at cryopreservation Homozygous
PCR Genotyping Protocol Genotyping_Protocol_QZ.pdf
Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome. (1996) J Cell Biol 135: 1403-13 (Added 5/19/2020)
PMID: 8947561

Background Strain Information

Strain Type Congenic Strain
Chimera/Founder Genetic Background C57BL/6J
Cryopreservation Strain Background (VCMR) C57BL/6J
Viability and Fertility Data

Homozygous viable and fertile.  Average litter size is about 8.  

Additional Information

Average litter size is about 8 for TgKO mice on the C57Bl6/J (B6) background. B6.TgKO mice are viable and fertile and survive beyond than 18 months of age.

In COL4A3/COL4A4 Tg mice, the incorporation of human α3(IV) collagen protein in the mouse GBM is significantly reduced in the presence of at least one normal mouse Col4a3 gene (i.e., in Col4a3+/+ or Col4a3+/- mice), but greatly increased in Col4a3-/- Alport mice.

B6.Col4a3-/- mice have a kidney phenotype recapitulating human Alport syndrome and develop progressive kidney disease (initially manifesting as proteinuria) which leads to kidney failure by 6-8 months of age. Expression of human COL4A3/COL4A4 transgene (Tg) on the Col4a3-/- background (KO) restores the expression of α3α4α5(IV) collagen in the glomerular basement membrane and largely rescues the Alport kidney phenotype in TgKO mice. Although proteinuria and abnormal kidney histology (glomerulosclerosis) can be observed after 6 months of age), B6.TgKO mice survive with apparent normal kidney function until 18-24 months of age.

(Note: COL4A3/COL4A4 Tg delays but does not prevent Alport-like kidney disease in Col4a3-/- on the 129 or SJL background, which could provide a model of late-onset Alport syndrome).