Teacher guide

Predict

A baby mouse usually comes from one egg and one sperm. Scientists in Tokyo tried to grow a mouse from the DNA of two mouse eggs and no sperm. Could two eggs and no sperm ever make a living mouse?

Circle one. Yes / No

Watch

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

Word of the day

Imprinting (im-PRIN-ting). In genetics, a tag on a gene that marks which parent the gene came from. The tag controls whether that copy of the gene switches on.

• A printing press presses inked letters onto paper. Print comes from an Old French word that means “to press.”
• Baby ducks imprint on the first big moving thing they see, and that’s usually their mom. English picked up the word imprinting in 1937 for this kind of fast learning.

Questions

1. An embryo is a baby animal at its earliest stage. Eggs and sperm carry the same genes. But put the DNA of two ordinary eggs together, and the embryo stops growing. If the genes are the same, why does a two-egg embryo stop growing?

   Hint. In the video, Raven says dad tags often push growth up. Where do dad tags come from?

2. A clone is an exact copy of one animal’s DNA. Kaguya had no dad. Her DNA came from the eggs of two different female mice, a newborn and an adult. Is Kaguya a clone of either mouse that gave her DNA?

   Circle one. Yes, of the newborn mouse / Yes, of the adult mouse / No, of neither mouse

   Hint. A clone gets all of its DNA from one animal. How many mice gave Kaguya DNA?

3. Raven names Prader-Willi syndrome in the video. Many kids born with this health condition are missing a few genes from dad’s chromosome 15. A chromosome is a long strand of DNA that holds many genes. These kids still have mom’s copy of those genes. Why can’t mom’s copy of those genes fill in for dad’s missing copy?

   Hint. In the video, Raven says only one parent’s copy of some genes is supposed to switch on. What happens to the other copy?

4. It took about 460 tries to make one adult mouse, Kaguya. In 2004, scientists said this method was far from being used in people. Why was a two-egg baby still far from use in people in 2004? Give two reasons.

   Hint. First, count the tries the scientists needed. Then think about the two changes the eggs needed.

Exit ticket

Predict

A baby mouse usually comes from one egg and one sperm. Scientists in Tokyo tried to grow a mouse from the DNA of two mouse eggs and no sperm. Could two eggs and no sperm ever make a living mouse?

Circle one. Yes / No

Watch

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

Word of the day

Imprinting (im-PRIN-ting). In genetics, a tag on a gene that marks which parent the gene came from. The tag controls whether that copy of the gene switches on.

• 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 (JEE-nohm) means a full set of an organism’s chromosomes. It comes from German Genom, a blend of Gen, “gene,” and Chromosom, “chromosome.” Scientists call this lesson’s word genomic imprinting.

Questions

1. Eggs and sperm carry the same genes, yet embryos made from two ordinary eggs stop growing. In the video, Raven talks about a growth gene and the piece of DNA that holds its switch. She says dad tags often push growth up. Why does a two-egg embryo stop growing? Go step by step, and use the growth gene as your evidence.

   Hint. Which tag can an egg never put on the growth gene’s switch? What does the switch do without that tag?

2. Kaguya had no dad. Her DNA came from the eggs of two different female mice, a newborn and an adult. Why isn’t Kaguya a clone of either mouse that gave her DNA? Use how much of a full set of chromosomes each egg carried as your evidence. Then say what a clone of the adult mouse would carry instead.

   Hint. Count how many mice gave Kaguya chromosomes and how much each mouse gave.

3. MedlinePlus Genetics reports two main causes of Prader-Willi syndrome. About 70% of cases come from a missing piece of dad’s chromosome 15. About 25% come from two copies of mom’s chromosome 15 and none from dad. One cause is a missing piece of dad’s chromosome 15. The other is two copies of mom’s chromosome 15. How can two different causes lead to the same condition? Use gene tags in your answer.

   Hint. For each cause, ask which parent’s copy of the chromosome 15 genes the child is missing.

4. Kaguya’s team made about 460 tries. Those tries gave 10 live pups, and one pup grew to adulthood. Out of roughly 460 tries to make Kaguya, what percent gave a live pup? What percent gave an adult mouse?

   Hint. Divide each count by the number of tries. Then multiply by 100.

5. About 460 tries gave one adult mouse. Kaguya also needed two changes. One egg came from a newborn mouse, and that same egg was missing the growth gene switch. In 2004, scientists said this method was far from use in people. Why was the two-egg method still far from use in people in 2004? Give two reasons. Use Kaguya’s success rates and the two changes her embryo needed.

   Hint. Think about what each change would mean for a human egg.

Claim, evidence, reasoning

Going further: a switch from mom or dad

1. A switch next to the growth gene blocks it unless the switch carries a dad tag, and only sperm add that tag. In 1995, a team at Princeton bred mice missing the growth gene switch on one copy of their DNA. Mice that got the missing switch from their mother were 27% heavier than mice that got the missing switch from their father. Why were the Princeton mice heavier when the missing growth gene switch came from mom instead of dad?

   Hint. Start with dad’s copy of the growth gene. Does its switch block the gene to begin with?

2. The Princeton mice and Kaguya both come from experiments on gene tags in mice. What’s one question you’d ask next about how gene tags pass from parents to offspring?

   Hint. What do these mouse studies leave unanswered?

Exit ticket

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.

Exit ticket