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.
George Q. Daley, Children's Hospital Boston
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.
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 Name||targeted mutation 1.1, George Q Daley|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1.1, George Q Daley; Lin28atm1.1Gqda|
|Gene Symbol and Name||Lin28a, lin-28 homolog A (C. elegans)|
|Gene Synonym(s)||LIN-28; LIN28; CSDD1; AL024421; expressed sequence AL024421; ZCCHC1; Lin28; lin-28 homolog (C. elegans); RGD1566408; Tex17; lin-28A; testis expressed gene 17; Tex17; Lin28; Lin-28|
|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.|
Heterozygotes are viable and fertile. Most homozygotes die within 1 day of birth, many having a cardiac ventricular septal defect.
When using the STOCK Lin28atm1.1Gqda/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023916 in your Materials and Methods section.
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