Kaguya the Mouse

Watch

1. 2 eggs can make a mouse, with some helpyoutube.com/shorts/1ymhrjaj6e0

Word of the day

Imprinting (im-PRIN-ting). In genetics, marking a gene copy with DNA methylation according to the parent it came from. For an imprinted gene, only the maternal copy or only the paternal copy is expressed.

• A printing press presses inked letters onto paper. Print comes from an Old French word meaning “to press.”
• In animal behavior, ducklings imprint on the first large moving object they see, usually their mother. English took the word imprinting in 1937 for this kind of fast learning.

Bonus word. Genome (from German Genom, a blend of Gen, “gene,” and Chromosom, “chromosome”) describes an organism’s full set of chromosomes. Biologists call this lesson’s word genomic imprinting.

Predict

1. In the video, Raven says 192 transferred embryos gave three pups and one adult mouse. A blastocyst is an early embryo ready for transfer into a foster mother. Make a guess before you open Wei’s 2022 paper. What percent of the edited eggs in Wei’s study do you think grew into blastocysts in the dish? Give your reason in one sentence.

   Hint. Think about when embryos made from eggs alone usually fail, in the dish or later in pregnancy.

Read the paper

Wei and others, “Viable offspring derived from single unfertilized mammalian oocytes,” Proceedings of the National Academy of Sciences, 2022. The paper is free to read.

Wei’s paper describes a different experiment from Kaguya’s. Kaguya came from the DNA of two eggs. Wei’s team made a mouse from one unfertilized egg by rewriting DNA methylation tags at seven imprinting control regions. They added a dad tag to one copy of two regions and stripped the mom tag from one copy of five more regions. Table 1 of the paper follows those embryos from the dish to adulthood.

1. Quantitative reasoning Table 1 follows 227 rebuilt eggs from the dish to adulthood. All 14 foster mothers became pregnant. Go down Table 1. What percent of embryos made it through each step, and which step lost the most? All 14 foster mothers got pregnant. What does that tell you about when most embryos were lost? What other counts would you need to know for sure when they were lost?

   Hint. Divide each count by the count in the row above. A pregnancy shows that at least one embryo implanted.

2. Process of science Rewriting only the two dad-tag regions, H19 and Gtl2, let no embryo reach day 13.5 (Figure 1D). Rewriting all seven gave 13 fetuses with heartbeats at day 13.5 from 158 transferred blastocysts. When the team checked tags, 2 of the 6 fetuses they tested and 1 of the 3 newborns carried correct tags at all seven regions. Seven-region editing rarely worked. Which explanation do the tag checks on fetuses and newborns support? What experiment would test that explanation?

   Hint. Compare how many embryos carried correct tags at all seven regions with how many survived.

3. Information flow After birth, the one adult mouse weighed about 19.8% less than controls. The team suspected Rasgrf1, a third dad-tag region they had not rewritten. Adding Rasgrf1 as an eighth region gave 2 pups from 155 transferred blastocysts, and both gained weight like wild-type mice. The adult mouse later mated with a male, and brains from three of her pups made normal amounts of Rasgrf1. How could a missing dad tag at the Rasgrf1 control region slow a mouse’s growth after birth? And why did the pups of Wei’s adult mouse make normal amounts of Rasgrf1?

   Hint. Ask which parent’s copy of Rasgrf1 switches on with a dad tag. Then ask where each pup’s two copies came from.

4. Science and society Wei’s team writes that parthenogenesis in mammals opens opportunities in agriculture, research and medicine. A farmer wants to use single-egg parthenogenesis on livestock next year. What would you tell them? Write a one-paragraph reply with numbers from Wei’s paper and one limit the authors name in their Discussion.

   Hint. Compare the success rates from both rounds of editing. Then read the Discussion for what the authors say still needs study.

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