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Kaguya the Mouse, College

2 eggs can make a mouse, with some help

In 2004, scientists in Japan reported a mouse named Kaguya, made from two eggs and no sperm. Some genes carry a tag that says which parent they came from, so two eggs alone cannot make a mouse. One egg came from a newborn mouse whose tags weren’t on yet. That mouse came from a line of mice born missing the piece of DNA that holds the switch for a growth gene.

A white lab mouse held in a scientist’s gloved hand
A printing press presses inked letters onto paper. Print comes from an Old French word meaning “to press.”

Your word of the day is

im-PRIN-ting

im-in, into, onfrom Latin in-
printto pressfrom Latin premere
-ingthe action or processfrom Old English -ing

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.

The head and face of a 13-day-old mouse embryo under a microscope

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.

A scientist in a lab coat looks through a microscope

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.

Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
A model of the twisted DNA double helix

Table 1 of Wei’s 2022 paper starts with 227 rebuilt eggs, and 192 grew to blastocysts in the dish.

In Wei’s Table 1, ____ of the 227 rebuilt eggs grew to blastocysts in the dish.

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
A scientist holds up a glass jar with a lab mouse inside

Wei’s team transferred 192 blastocysts, and 3 became live pups at day 19.5.

In Wei’s Table 1, ____ of the 192 transferred embryos became live pups.

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Black-and-white video of a small house mouse sniffing around in the corner of a wall

Which step in Table 1 of Wei’s paper lost the most embryos?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Close-up video of a brown mouse with big ears sitting in a ceramic dish, nibbling sunflower seeds

All 14 foster mothers that received Wei’s embryos became pregnant.

What do 14 pregnancies from 14 foster mothers tell you about when Wei’s embryos were lost?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Video of a scientist in a lab placing and studying a specimen slide under a microscope

After seven-region editing, only 2 of 6 fetuses tested and 1 of 3 newborns carried correct tags at all seven regions.

Which explanation for the low success of Wei’s seven-region editing do the tag checks on fetuses and newborns support?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Video of a scientist's gloved hand using a pipette to load samples into a gel for a DNA experiment

Which experiment would test whether incomplete editing explains the low success of Wei’s seven-region method?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Animation of a glowing golden DNA double helix slowly turning against a dark blue background

Wei’s one adult mouse weighed about 19.8% less than controls, and the team suspected Rasgrf1, a dad-tag region they had not rewritten.

How could a missing dad tag at the Rasgrf1 control region slow a mouse’s growth after birth?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Several white mice in a cage, one sitting inside a round metal food dish

Wei’s adult mouse later had pups with a normal male, and the pups made normal amounts of Rasgrf1.

Why did the pups of Wei’s adult mouse make normal amounts of Rasgrf1?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Two lab mice on a purple-gloved hand: a brown gene-knockout mouse beside a normal black lab mouse

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. Based on Wei’s numbers, what should the farmer hear?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
Black-and-white photo of a woman scientist in a lab coat looking at a white mouse inside a labeled glass jar

Which limit do Wei’s authors name in the Discussion of their 2022 paper?

See the table
Step in Table 1CountPercent of the step before
Rebuilt eggs (an egg plus its own first polar body)227Starting count
Grew to blastocysts in the dish192
Transferred into 14 foster mothers, all 14 pregnant192
Live pups at day 19.5 of pregnancy3
Pups that grew to adulthood1
A white mother mouse curled over her nursing babies inside a small wooden house lined with straw

Table 1 of Wei’s 2022 paper follows edited eggs from the dish to adulthood.

Which summary fits Table 1 of Wei’s 2022 paper?

A big litter of pink newborn baby mice piled together in a straw nest

Which question can’t Table 1 of Wei’s paper answer?

A brown wild mother mouse with several young mice gathered under her among fallen leaves

Lesson complete

Today’s word

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.

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Sources
  1. Tomohiro Kono and colleagues, Tokyo University of Agriculture, Nature, 2004
  2. Philip Leighton, Shirley Tilghman and colleagues, Princeton University, Nature, 1995
  3. Andrew Keniry, Wolf Reik and colleagues, Nature Cell Biology, 2012
  4. Yayoi Obata, Tomohiro Kono and colleagues, Development, 1998
  5. Manabu Kawahara, Tomohiro Kono and colleagues, Nature Biotechnology, 2007
  6. Yanchang Wei, Cai-Rong Yang and Zhen-Ao Zhao, Shanghai Jiao Tong University and UC San Francisco, PNAS, 2022
  7. Review by Denise Barlow and Marisa Bartolomei, Cold Spring Harbor Perspectives in Biology, 2014
  8. MedlinePlus Genetics, US National Library of Medicine, Prader-Willi, Angelman, Beckwith-Wiedemann
  9. Helen Pearson, “Mouse created without father”, Nature News, April 22, 2004
  10. John Travis, “Two egg cells make fatherless mouse”, Science News, May 2004
  11. Vision and Change core concepts and competencies, as summarized in Brownell and others, CBE Life Sciences Education, 2014
  12. Word origins from Dictionary.com: imprinting, imprint, in-, print, -ing, genome, press, pressure, impression, impressionism, espresso
  13. Spanish and French words from Wiktionary: imprimir, imprimer