STOCK Lin28a^tm1.1Gqda/J

Stock number: 023916
Research areas: Developmental Biology Research, Internal/Organ Research, Metabolism Research

Description

These mice carry a germline knockout of the Lin28a (lin-28 homolog A (C. elegans)) gene. Homozygous mice show dwarfism and most die within 1 day of birth (many showing cardiac ventricular septal defects). Survivors exhibit decreased bone mineral density.

Detailed description

LIN28A (lin-28 homolog A (C. elegans)) is an RNA-binding protein that blocks biogenesis of Mirlet7 (let-7) microRNAs. Let-7 targets are known regulators of mammalian body size and metabolism.

These mice carry a germline knockout of the Lin28a gene. Homozygous mice show dwarfism as early as E13.5 and by E18.5 demonstrate a 20% reduction in weight relative to heterozygous controls. Although born at expected Mendelian ratios, roughly 93% of Lin28a knockout mice die within 1 day of birth (2 out of 5 mice harboring a cardiac ventricular septal defect). Those animals that survive are 30-50% smaller in weight and 20-30% shorter in length than controls. Dual-energy x-ray absorptiometry imaging confirms a decreased fat mass and also reveals decreased bone mineral density in the knockout animals, suggesting that these animals suffer from metabolic dysregulation.

Development

Exon 2 was flanked by loxP sites and an FRT-flanked neomycin cassette was introduced through homologous recombination in (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells. Mice were crossed to inbred C57BL/6 for ten generations then bred with FVB background germline-specific Ddx4-cre mice (see Stock No. 006954) to excise the floxed region. The neomycin cassette was excised. The donating investigator reported that this strain was backcrossed to FVB for 8 generations (see SNP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 19 markers across 13 chromosomes were found to be segregating, suggesting an incomplete backcross.

Allele

Symbol: Lin28a^tm1.1Gqda
Name: targeted mutation 1.1, George Q Daley
MGI accession ID: MGI:5500060
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lin28a
Marker name: lin-28 homolog A (C. elegans)
Chromosome: 4
Strain of origin: (C57BL/6 x 129S4/SvJae)F1
Molecular note: A loxP site was inserted upstream of exon 2. An FRT flanked neo cassette with a 5' loxP site was inserted downstream of exon 2 via homologous recombination. Cre-mediated recombination removed exon 2.