CBACa.129S4(B6)-Ldah^tm1Mrtn/J

Stock number: 029781
Product name: Ldah^-
Research areas: Cancer Research, Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research, Sensorineural Research

Description

Ldah^-/- mice have a frt- and loxp-flanked βgeo cassette disrupting the expression of the lipid droplet associated hydrolase (Ldah) gene. These mice may be useful for studying lipid pathways associated with prostate oncogenesis.

Detailed description

Ldah^-/- mice have a βgeo cassette disrupting the expression of the lipid droplet associated hydrolase (Ldah) gene. The inserted cassette is flanked with four pairs of incompatible recombination sequences (frt, F3, loxP, and lox511) which allow for FLP and Cre recombination. LDAH is associated with a risk for early-onset prostate cancer (PCa). Homozygotes are viable and fertile. Ldah^-/- males develop increased numbers of prostate intraepithelial neoplasia (PINs) as well as invasive prostate lesions. These mice also exhibit hearing loss, and mild to moderate obesity in females at advanced ages.

Breeding these mice to mice expressing Flp or Cre recombinase restores the expression of wildtype Ldah.

Development

A targeting vector was designed to insert a strong splice acceptor (SA), β-galactosidase/neomycin phosphotransferase fusion gene (βgeo) and poly-A tail (pA) downstream of exon 2 of the lipid droplet associated hydrolase (Ldah) gene. The inserted cassette is flanked with four pairs of incompatible recombination sequences (frt, F3, loxP, and lox511). The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. Resulting Ldah^-/- offspring were subsequently bred to CBA/CaJ mice (Stock No. 000654) for at least 7 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize CBA/CaJ oocytes.

Allele

Symbol: Ldah^tm1Mrtn
Name: targeted mutation 1, Cynthia Morton
MGI accession ID: MGI:5804186
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Ldahⁱ
Marker symbol: Ldah
Marker name: lipid droplet associated hydrolase
Marker synonyms: 1110057K04Rik; C2orf43; hLDAH; RGD1311648
Chromosome: 12
Strain of origin: 129S4/SvJae
Expressed genes: Bgeo,fusion of beta-galactosidase and neomycin phosphotransferase genes,E. coli
Site of expression: When bred to mice expressing Flp or Cre recombinase, expression of wildtype Ldah is restored.
Molecular note: A targeting vector was designed to insert a strong splice acceptor (SA), beta-galactosidase/neomycin phosphotransferase fusion gene (betageo) and poly-A tail (pA) downstream of exon 2 of the gene. The inserted cassette is flanked with four pairs of incompatible recombination sequences (frt, F3, loxP, and lox511) resulting in an alternatively spliced product that does not encode the full length protein. Western blot of multiple tissues confirmed that no protein is expressed in mutant mice.