Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
The Baby Mateo Case
Experimental Design domainBiomedical Innovations (BI)Lesson 11 of 20Your seat: Principal Investigator (with the lab's animal-welfare liaison)
When Is a Mouse a Good Stand-In for Mateo?
Discovery question
When does studying a mouse actually teach us something true about Mateo, and when does it fool us?
💡 A model is judged on two separate kinds of good: whether it breaks the same cause () and whether it looks like the disease (), and animal work is governed by .
The plan
Prerequisite check
Before this page, you should know
- is programmable: a guide RNA matches a chosen and directs the Cas9 to cut there, and the cell's repair can be steered to knock a gene out, knock one in, or install a single point .
- To target a new site you only redesign the guide RNA, not rebuild a whole animal, so is far faster than older methods.
If not, review
Today's new idea is only
A model is judged on two separate kinds of good: whether it breaks the same cause () and whether it looks like the disease (), and animal work is governed by .
Learn first
What you will learn
Goal: Judge a proposed mouse study by and , and apply (Replacement, Reduction, Refinement) and ARRIVE reporting to decide whether the model can honestly answer a human question.
Know by the end
- An is a non-human organism studied to learn about a human condition; it is a stand-in, never the disease itself.
- asks whether the model disrupts the same cause (gene or pathway) believed to act in humans; asks whether the model looks like the human disease.
- Penetrance is the percent of mutant animals that actually show the phenotype; in the real Ezh2 study only about 20% of mutant mice were born with a .
- (Replacement, Reduction, Refinement) and the govern and report animal research; Reduction is a statistics and power idea, not only a kindness idea.
Learn first
Model: A real mouse cleft-palate study, plus two ways to call a model good
A team studied a gene called Ezh2 in the developing . They could not delete it from the whole mouse, because losing it everywhere kills the before the palate even forms. So they deleted it only in the cells lining the roof of the mouth, only during palate building, and collected at embryonic day 14.0, just before the shelves lift and fuse. About 20% of the mutant mice were born with a palate; the other 80% closed normally. A mouse is even on the table because mouse and human palates are built by the same basic script: shelves grow down beside the tongue, lift to , then meet and fuse at the .
Now read two claims about a mouse model of clefting. Claim A: the mouse is good because the gene knocked out is the same pathway suspected in human clefts. Claim B: the mouse is good because the mutant pups are actually born with a visible , like a human. These are two different kinds of good. One is about matching the cause. The other is about matching the look.
Do the work
Explore (work the model before reading on)
- In the model, why could the team not delete Ezh2 from the whole mouse?
- What fraction of mutant mice actually showed a , and what happened to the rest?
- Put each claim in your own words: what is Claim A really claiming, and what is Claim B really claiming?
- The 20% number is a problem for one of those two claims more than the other. Which one, and why?
- Suppose a mouse model perfectly reproduces a human (Claim B is strong) but the gene knocked out has nothing to do with the human pathway (Claim A is weak). Would that model help us understand Mateo? Explain.
The plan
Guided notes
1
Two kinds of good, named
Model start: A model is never the disease itself, so we judge how trustworthy the stand-in is on two separate axes, not one.
- asks whether the model breaks the same ____ (gene or pathway) we think acts in humans.
- asks whether the model ____ like the human disease, an actual you can see.
- In the Ezh2 study only about 20% of mutants showed a , which ____ (lowers / raises) the , and is exactly why scientists report the penetrance instead of pretending every animal clefts.
2
The 3Rs and ARRIVE
- Replacement: use a non-animal method (cells, computer models) when it can answer the question ____ animals.
- Reduction: use the ____ number of animals that still gives a valid answer; this connects directly to sample-size and power planning.
- ARRIVE exists because audits found randomization reported in only 30 to 40% of animal papers and sample-size justification in under ____ %.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Sun et al. 2023, Ezh2 methylation in oral epithelia promotes palatogenesis (Birth Defects Res)
Why this source matters
This is the published evidence behind today's idea: A model is judged on two separate kinds of good: whether it breaks the same cause () and whether it looks like the disease (), and animal work is governed by .
Words to unlock first
animal modelface validityconstruct validitythe 3RsARRIVE guidelines
Reading moves
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Stop point
You do not need the methods or statistics yet. If a sentence is about lab technique or math you have not learned, mark it and skip it.
Your output
Write one claim-evidence sentence: what this source claims, and the one piece of evidence that backs it up.
Where this fits
Tested on (Ohio WebXam)
Genetics of Disease · 072130
PLTW lesson
MI · Experimental Design domain · Model design and validity; the 3Rs and ARRIVE reporting in animal research
WebXam domain
Bio-Molecular Technology
Evidence to produce
A junior researcher proposes: knock out a human cleft-pathway gene in 200 mice and see if they cleft. As PI, write three short notes back: (1) Validity: does this aim for construct validity, face validity, or both, and what is your evidence? (2) The 3Rs: name one R this proposal ignores and how to fix it (hint: where did 200 come from?). (3) Mateo link: if 20% of these mice cleft, what could you and could you not claim about a real human like Mateo?
Lab / skill
Biomedical Innovations (BI) · AP Biology
Words
Vocabulary (the same words your classes use)
The plan
Track your progress today
Check these off as you work through the lesson, then submit. This tells Mr. Mendoza how you're doing so he can help the class. It does not replace turning in your producible.
Use the code Mr. Mendoza gave you, not your name. Saved on this device.
Check off as you finish
- Read the Model and answered the Explore questions.
- Filled in the guided notes in my own words.
- Defined the new vocabulary with an example.
- Built the producible: A junior researcher proposes: knock out a human cleft-pathway gene in 200 mice and see if they cleft. As PI, write three short notes back: (1) Validity: does this aim for construct validity, face validity, or both, and what is your evidence? (2) The 3Rs: name one R this proposal ignores and how to fix it (hint: where did 200 come from?). (3) Mateo link: if 20% of these mice cleft, what could you and could you not claim about a real human like Mateo?
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
Check yourself
Exit ticket (Claim, Evidence, Reasoning)
- Claim: A mouse (is / is not) a reasonable starting model for studying how Mateo's formed.
- Evidence: Cite one fact about the shared script and one fact about the ____ % penetrance in the Ezh2 study.
- Reasoning: Explain how and together support your claim, and name one limitation the partial penetrance forces you to admit.
How this is graded (rubric)
For: A junior researcher proposes: knock out a human cleft-pathway gene in 200 mice and see if they cleft. As PI, write three short notes back: (1) Validity: does this aim for construct validity, face validity, or both, and what is your evidence? (2) The 3Rs: name one R this proposal ignores and how to fix it (hint: where did 200 come from?). (3) Mateo link: if 20% of these mice cleft, what could you and could you not claim about a real human like Mateo?
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in the right way (Schoology for routine work) and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
How the model answer scores against this rubric
- CompleteProficient: Nothing is left blank: the model fills every part of "A junior researcher proposes: knock out a human cleft-pathway gene in 200 mice and see if they cleft. As PI, write three short notes back: (1) Validity: does this aim for construct validity, face validity, or both, and what is your evidence? (2) The 3Rs: name one R this proposal ignores and how to fix it (hint: where did 200 come from?). (3) Mateo link: if 20% of these mice cleft, what could you and could you not claim about a real human like Mateo?".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be turned in on Schoology and confirmed.
Explore
Where this leads: careers
Principal Investigator Laboratory Animal Veterinarian Developmental Biologist
What's next: We decided a mouse can be a fair stand-in when its construct and hold up. But knocking out a gene and seeing a is not yet proof the gene caused it; something else changed by the same edit could be to blame. So next: how do we prove the gene itself, and nothing else, caused the cleft? We chase that next time.