Popular transgenic and mutant animals used in pharmacology MCQs With Answer

Introduction: Transgenic and mutant animals — including knockout, knock‑in, conditional, humanized and reporter models — are indispensable in pharmacology for studying drug targets, pharmacodynamics, pharmacokinetics and disease mechanisms. B.Pharm students must understand common models such as ApoE-/-, LDLR-/-, ob/ob, db/db, APP/PS1, NSG and hACE2 mice, zebrafish mutants and Drosophila models, plus technologies like CRISPR/Cas9, Cre‑LoxP, and reporter genes (GFP, luciferase). This knowledge helps in model selection, interpreting efficacy/toxicity data, genotyping, phenotyping and appreciating limitations, ethical concerns and translational relevance. Clear familiarity with these models improves drug screening and translational study design. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which animal model is most commonly used to study atherosclerosis and lipid metabolism in pharmacology?

• ApoE knockout (ApoE-/-) mice
• ob/ob (leptin-deficient) mice
• SCID mice
• Tg2576 Alzheimer’s mice

Correct Answer: ApoE knockout (ApoE-/-) mice

Q2. Which genetic system is most widely used to generate conditional (tissue-specific or inducible) gene deletions in mice?

• Cre-LoxP recombination system
• RNA interference (RNAi)
• Random transgenesis by pronuclear injection
• Transposon-based insertion

Correct Answer: Cre-LoxP recombination system

Q3. For studying human drug metabolism in vivo, which transgenic model expressing human cytochrome P450 enzymes is most appropriate?

• Humanized CYP3A4 transgenic mice
• nude mice
• APP/PS1 transgenic mice
• Zebrafish Tg(fli1:GFP)

Correct Answer: Humanized CYP3A4 transgenic mice

Q4. Which reporter gene is preferred for non‑invasive, whole‑body bioluminescent imaging in live small animals?

• Firefly luciferase (luc)
• Green fluorescent protein (GFP)
• β-galactosidase (LacZ)
• Neomycin resistance gene (neo)

Correct Answer: Firefly luciferase (luc)

Q5. Knockout of Rag1 or Rag2 genes in mice results primarily in which phenotype useful for pharmacology?

• Severe combined immunodeficiency with absence of mature B and T cells
• Obesity and hyperphagia
• Spontaneous atherosclerosis
• Enhanced pain sensitivity

Correct Answer: Severe combined immunodeficiency with absence of mature B and T cells

Q6. What is the major cause of off-target editing in CRISPR/Cas9 genome engineering?

• Mismatches between guide RNA and unintended genomic sites
• Integration of donor plasmid at the Rosa26 locus
• Cre recombinase-mediated excision errors
• Excessive luciferase expression

Correct Answer: Mismatches between guide RNA and unintended genomic sites

Q7. Which transgenic mouse model is commonly used to study Alzheimer’s disease pathology and test anti‑amyloid drugs?

• APP/PS1 double transgenic mice
• NSG immunodeficient mice
• ob/ob mice
• LDLR knockout mice

Correct Answer: APP/PS1 double transgenic mice

Q8. Which immunodeficient mouse strain is most suitable for engrafting human tumor cells for xenograft pharmacology studies?

• NSG (NOD‑SCID‑IL2Rγnull) mice
• Sprague‑Dawley rats
• C57BL/6 wild‑type mice
• DBA/2 mice

Correct Answer: NSG (NOD‑SCID‑IL2Rγnull) mice

Q9. What is a primary advantage of zebrafish mutants in drug discovery and toxicity screening?

• Transparent embryos enabling rapid in vivo imaging and high‑throughput screens
• Long lifespan for chronic toxicity studies
• Close physiological similarity to human immune responses
• Large body mass for repeated blood sampling

Correct Answer: Transparent embryos enabling rapid in vivo imaging and high‑throughput screens

Q10. Which mutant mouse is characterized by leptin deficiency and is commonly used to study obesity and metabolic drugs?

• ob/ob mice (leptin-deficient)
• db/db mice (leptin receptor-deficient)
• ApoE-/- mice
• NOD mice

Correct Answer: ob/ob mice (leptin-deficient)

Q11. In a Tet‑On inducible transgenic system, which molecule is used to activate transgene expression?

• Doxycycline
• Tamoxifen
• IPTG
• Isopropyl β‑D‑1‑thiogalactopyranoside

Correct Answer: Doxycycline

Q12. What best defines a knock‑in animal model?

• Precise insertion of a specific gene or mutation into a defined genomic locus
• Random integration of a transgene into the genome
• Complete deletion of a gene’s coding sequence
• Transient knockdown by siRNA

Correct Answer: Precise insertion of a specific gene or mutation into a defined genomic locus

Q13. Which molecular technique has been a gold standard to determine transgene copy number and integration pattern in founder animals?

• Southern blot analysis
• Western blot analysis
• ELISA
• Flow cytometry

Correct Answer: Southern blot analysis

Q14. Deletion of the LDL receptor (LDLR) gene in mice typically results in which phenotype used in cardiovascular pharmacology?

• Hypercholesterolemia and accelerated atherosclerosis
• Severe combined immunodeficiency
• Neurodegeneration similar to Parkinson’s disease
• Resistance to diet‑induced obesity

Correct Answer: Hypercholesterolemia and accelerated atherosclerosis

Q15. Which ethical principle summarizes replacement, reduction and refinement for animal research?

• The 3Rs framework
• Good Laboratory Practice (GLP)
• Declaration of Helsinki
• ARRIVE guidelines

Correct Answer: The 3Rs framework

Q16. Which immunodeficient mouse strain is widely used to generate humanized immune system mice for immunopharmacology studies?

• NSG mice (NOD‑SCID‑IL2Rγnull)
• FVB/N mice
• Wistar rats
• Swiss albino mice

Correct Answer: NSG mice (NOD‑SCID‑IL2Rγnull)

Q17. Which reporter requires administration of an exogenous substrate to produce a detectable signal in vivo?

• Luciferase (requires luciferin substrate)
• GFP (intrinsic fluorescence)
• LacZ (requires X‑Gal staining ex vivo)
• β‑actin reporter (endogenous protein)

Correct Answer: Luciferase (requires luciferin substrate)

Q18. What does mosaicism in founder transgenic animals mean?

• The founder has a mixture of edited and unedited cells in different tissues
• The transgene is present at a single fixed copy number
• All offspring will be homozygous for the transgene
• The transgene is restricted to germ cells only

Correct Answer: The founder has a mixture of edited and unedited cells in different tissues

Q19. Which genome editing approach has greatly accelerated generation of knockout rats for pharmacology studies?

• CRISPR/Cas9
• Embryonic stem cell homologous recombination (classic mouse method)
• Random chemical mutagenesis (ENU)
• Pronuclear injection of linearized plasmid without targeting

Correct Answer: CRISPR/Cas9

Q20. Which transgenic mouse expressing human ACE2 is used to model SARS‑CoV‑2 infection and test antivirals?

• hACE2 transgenic mice
• ob/ob mice
• ApoE-/- mice
• CBA/J mice

Correct Answer: hACE2 transgenic mice

Q21. Which species is most commonly used in behavioral pharmacology and preclinical psychopharmacology studies?

• Rats (e.g., Wistar, Sprague‑Dawley)
• Zebrafish
• Guinea pigs
• Fruit flies (Drosophila)

Correct Answer: Rats (e.g., Wistar, Sprague‑Dawley)

Q22. What does the acronym PDX stand for in oncology pharmacology models?

• Patient‑derived xenograft
• Protein‑drug interaction Xchange
• Promoter‑driven Xenoexpression
• Pharmacodynamics Xenoassay

Correct Answer: Patient‑derived xenograft

Q23. In a Cre‑loxP system, if two loxP sites are in the same orientation on a chromosome, what is the likely outcome when Cre recombinase is expressed?

• Deletion of the intervening DNA segment
• Duplication of the intervening sequence
• Inversion of the intervening DNA
• No recombination occurs

Correct Answer: Deletion of the intervening DNA segment

Q24. Targeted deletion of the tumor suppressor p53 in mice typically leads to which research‑relevant phenotype?

• Increased susceptibility to spontaneous tumors
• Impaired glucose tolerance and obesity
• Severe immunodeficiency
• Enhanced wound healing

Correct Answer: Increased susceptibility to spontaneous tumors

Q25. Which inbred mouse strain spontaneously develops autoimmune diabetes and is used as a type 1 diabetes model?

• NOD (Non‑Obese Diabetic) mice
• NSG mice
• ApoE-/- mice
• Tg2576 mice

Correct Answer: NOD (Non‑Obese Diabetic) mice

Q26. Which phenomenon is a common limitation of random insertion transgenic animals and can affect expression levels?

• Position effect variegation due to insertion site
• Complete absence of founder mosaicism
• Guaranteed single‑copy insertion at a safe harbor locus
• Inability to produce any protein from the transgene

Correct Answer: Position effect variegation due to insertion site

Q27. Which model is best suited for studying human hepatic drug metabolism and human-specific hepatotoxicity?

• Humanized liver mice (e.g., uPA/SCID with human hepatocyte engraftment)
• Standard C57BL/6 mice
• ob/ob mice
• Wild‑type zebrafish

Correct Answer: Humanized liver mice (e.g., uPA/SCID with human hepatocyte engraftment)

Q28. Which laboratory method is most appropriate to confirm precise CRISPR-mediated edits at an intended genomic locus?

• Sanger sequencing of PCR amplicons spanning the target site
• Flow cytometry of peripheral blood cells
• Western blot for an unrelated protein
• Behavioral testing in open field

Correct Answer: Sanger sequencing of PCR amplicons spanning the target site

Q29. Which reporter assay is commonly used to quantify promoter activity in cell lines and transgenic constructs?

• Luciferase reporter assay
• Complete blood count (CBC)
• ELISA for albumin
• Mass spectrometry of lipids

Correct Answer: Luciferase reporter assay

Q30. Which strategy helps minimize off‑target effects when using CRISPR/Cas9 in generating mutant animals?

• Use high‑fidelity Cas9 variants and carefully designed guide RNAs
• Increase guide RNA length to >100 nucleotides
• Avoid sequencing the edited region to prevent artifacts
• Use random chemical mutagenesis instead of targeted design

Correct Answer: Use high‑fidelity Cas9 variants and carefully designed guide RNAs

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