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 knock-in mice express Lin28a under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter. These mice are larger than non-transgenic animals, show wider faces, larger ears, and coarser hair, even in the absence of tTA/rtTA/doxycyline induction. RT-PCR demonstrates that there is some ectopic expression of the transgene in both neonates and adults. In adults, there is a sevenfold increase in the level of Lin28a mRNA in skeletal muscle, a fivefold increase in the ovary, and fourfold increase in the hypothalamus.

Fasting and fed glucose levels are lower in transgenic mice. Both males and females clear glucose more efficiently. Transgenic mice also have increased insulin sensitivity and are resistant to age-induced and diet-induced obesity, as well as hepatosteatosis. Mice show markedly improved glucose tolerance and insulin sensitivity under high fat diet conditions. Transgenic mice achieve first estrus at day 31.8, as compared to day 27.3 in wildtype mice. Transgenic animals show an approximated 3 day delay to the date of the first litter. Overall fertility in mutant and wildtype mice is about the same over the first 3 months of life. 

Lin28a expression can be induced with doxycycline in progeny derived from a cross with a Gt(ROSA)26Sor M2-rtTA strain (see Stock No. <a href="https://www.jax.org/strain/006965">006965</a>). This leads to rapid death associated with marked gut pathology. Uninduced mice have thickened skin, larger bones and proportionately enlarged visceral organs.

Uninduced Gt(ROSA)26Sor M2-rtTA/tetO-Lin28a compound mutant mice are said to have the same phenotype as animals carrying only the tetO-Lin28a mutation.

These knock-in mice express Lin28a under the regulatory control of a Col1a1-driven tetO promoter. These mice are larger than non-transgenic animals, even in the absence of tTA/rtTA, show delayed estrus, and a resistance to age/diet-induced obesity.

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