Bwk (bilateral wasting kidneys) is a recessive mutation caused by a G to A point mutation in the Col4a4 (collagen, type IV, alpha 4) gene. Mice exhibit several characteristics of Alport Syndrome including glomerulosclerosis, albuminuria, tubular atrophy, tubulointerstitial nephritis and an accumulation of abnormal collagen in the glomerular basement membrane (GBM) as well as GBM lesions.
Read More +Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous (Hypomorph) | Col4a4 | collagen, type IV, alpha 4 |
Bwk (bilateral wasting kidneys) is a spontaneous recessive mutation caused by a G to A point mutation in the first base of intron 30 of the Col4a4 (collagen, type IV, alpha 4) gene. The mutation maintains the mRNA reading frame, but skips exon 30 resulting in low levels of collagen α 3 α 4 α 5 (IV) trimers that are secreted and incorporated into the glomerular basement membrane. Col4a4 encodes as subunit of type IV collagen, a structural component of basement membranes. Mutations in Col4a4 are associated with type II autosomal recessive Alport Syndrome (hereditary glomerulonephropathy). Mice exhibit the following characteristics: progressive elevated ACR (albumin to creatinine ratio), glomerulosclerosis, inflammatory cell infiltration in the kidneys tubular atrophy, podocyte foot process effacement, and tubular protein casts. Similar to a subset of Alport syndrome patients, mice develop an accumulation of abnormal collagen in the glomerular basement membrane (GBM) as well as GBM lesions. No hearing or eye pathologies are detected.
Of the three genetic backgrounds tested, mice on the DBA/2J (Stock No. 014079) genetic background exhibit higher ACR, earlier onset of protein casts and inflammatory cell infiltration as compared to the original mixed NZO/NON background (Stock No. 005326) and mice on the 129S1/SvImJ background. However,kidneys develop severe end stage renal disease by 12 weeks of age in both the DBA/2J and 129S1 backgrounds. This strain may be useful for studying Alport Syndrome and abnormal collagen IV structure.
The bilateral wasting kidneys (bwk) mutation arose spontaneously on the incipient recombinant congenic NONcNZO4/Lt (at N2F10) background at The Jackson Laboratory. This recessive mutation was first identified by a lean body type; it later was observed that mice developed chronic nephritis. The mutation was identified as a G to A point mutation in the first base of intron 30 of the Col4a4 (collagen, type IV, alpha 4) gene. The mutation occurred in the NON region of chromosome 1. Due to inbreeding depression mice of the recombinant congenic line were crossed to NON/ShiLtJ mice in order to succeed in maintaining it. Offspring of this cross were then intercrossed with N2F12 cousins to recover the bwk mutant subline. The mutant subline was then maintained by sibling inbreeding with cousin inbreeding in two generations. Sperm was cryopreserved from homozygous males at generation F45. The bwk allele was introgressed from NON;NZO-Col4a4bwk/J (Stock No. 005326) to 129S1/SvImJ for 6 generations. During backcrossing, the Y chromosome was fixed to the 129S1/SvImJ genetic background. Sperm was cryopreserved from homozygous males in 2012.
Allele Name | bilateral wasted kidneys |
---|---|
Allele Type | Spontaneous (Hypomorph) |
Allele Synonym(s) | bwk |
Gene Symbol and Name | Col4a4, collagen, type IV, alpha 4 |
Gene Synonym(s) | |
Strain of Origin | NONcNZO4/Lt |
Chromosome | 1 |
Molecular Note | The mutation was identified as a G to A subsitition in the first base of intron 30. As a result exon 30 is skipped, however, the mRNA reading frame is maintained. Protein and immunohistochemical analysis indicates some alpha4 is produced and forms low levels of collagen IV (alpha3, alpha4, alpha5) trimers. |
When using the bwk mouse strain in a publication, please cite the originating article(s) and include JAX stock #017865 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for NON(NZO)-Col4a4<bwk> |
Frozen Mouse Embryo | 129S1.NON(NZO)-Col4a4<bwk>/PgnJ | $2595.00 |
Frozen Mouse Embryo | 129S1.NON(NZO)-Col4a4<bwk>/PgnJ | $2595.00 |
Frozen Mouse Embryo | 129S1.NON(NZO)-Col4a4<bwk>/PgnJ | $3373.50 |
Frozen Mouse Embryo | 129S1.NON(NZO)-Col4a4<bwk>/PgnJ | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.