STOCK Lmx1b^tm4.1Rjo/J

Stock number: 031287
Product name: Lmx1b^lox
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Lmx1b^lox/lox mice possess loxP sites flanking exons 4-6 of the LIM homeobox transcription factor 1 beta gene. These floxed mice are useful for tissue-specific deletion of Lmx1b when studying the role of this gene in nail-patella syndrome.

Detailed description

Lmx1b^lox/lox mice possess loxP sites flanking exons 4-6 of the LIM homeobox transcription factor 1 beta (Lmx1b) gene. This part of the gene encodes the DNA-binding homeodomain. LMX1B is a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and the dopaminergic and serotonergic neurons. Mutations in the Lmx1b gene are commonly found in patients with nail-patella syndrome which is characterized by abnormalities of the nails, knees, elbows, and pelvis. Patients with nail-patella syndrome also exhibit kidney abnormalities including thickened glomerular basement membrane with fibrillar inclusions and electron-lucent areas as well as the disappearance of podocyte foot processes. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 4-6 deleted in the cre-expressing tissues.

When bred to mice expressing podocyte-specific Cre recombinase (NPHS2-cre; Stock No. 008205), the resulting offspring die 2 weeks after birth due to renal failure. Five days after birth, mice exhibit loss of podocyte foot processes, and this was accompanied by thickening of the glomerular basement membrane and focal-segmental glomerulosclerosis by six days of age.

Development

The Lmx1b^lox targeting vector was designed to insert loxP sites flanking exons 4-6 of the LIM homeobox transcription factor 1 beta (Lmx1b) gene. The construct also contained a loxP-flanked neomycin selection cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺-derived AB-1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a CMV-Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons 4-6, intact floxed-neo cassette, or excision of both exons 4-6 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exons 4-6, were injected into blastocysts and resulting chimeric males were bred with C57BL/6 females. Mice were then bred to R26R-YFP mice. Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664). The R26R-YFP allele was bred out of this stock.

Allele

Symbol: Lmx1b^tm4.1Rjo
Name: targeted mutation 4.1, Randy L Johnson
MGI accession ID: MGI:3714802
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Lmx1b^tm1Witz; Lmxb1^lox
Marker symbol: Lmx1b
Marker name: LIM homeobox transcription factor 1 beta
Marker synonyms: FSGS10; GENA 191; Icst; LMX1.2; NPS1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Molecular note: LoxP sites were inserted into introns 4 and 6, flanking sequence that encodes the homeodomain. The construct also contains a loxP-flanked neomycin selection cassette. A Cre expression plasmid was used to remove the floxed neo cassette.