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.
Exon 2 of the gene is flanked by loxP sites in this conditional targeted mutation strain. Cre excision of the floxed segment produces a knockout allele.
Muscle-specific knockout mice created through crosses with Myf5 (myogenic factor 5)-cre animals display glucose intolerance and reduced Insr (insulin receptor) expression.
Mice created from crosses with germline-specific Ddx4-cre mice (see Stock No. 006954) show dwarfism as early as E13.5 and by E18.5 show 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 the decreased fat mass and also revealed decreased bone mineral density in the knockout animals, suggesting that these animals suffer from metabolic dysregulation.
