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Course: MCAT > Unit 2

Lesson 1: Foundation 1: Biomolecules

Genetics: Cancer-causing NF1 mutations in mice


Neurofibromin is a protein encoded by the NF1 gene on chromosome 17. In humans, it contains multiple functional domains, including a Ras GTPase-activating protein-related domain (GRD), a cysteine-serine-rich domain (CSRD), and a central region with multiple binding sites for other proteins. Under normal circumstances, neurofibromin acts as a tumor suppressor in nerve cells, modulating Ras signaling by altering the ratio of active Ras-GTP to inactive Ras-GDP, which results in further alterations to the ERK signaling pathway.
Neurofibromatosis type 1 is caused by a mutation in the NF1 gene that results in skin hyperpigmentation and numerous neurofibromas, a type of benign cutaneous nerve sheath tumor. In rare cases a neurofibroma may turn into a malignant tumor, called a malignant peripheral nerve sheath tumor (MPNST), in a process known as malignant transformation. Researchers studied the phenotypic expression of neurofibromatosis in mice with NF1 mutations by performing the following experiments.
Experiment 1
Researchers created a large population of mice by initially mating a healthy female mouse with a homozygous diseased male mouse. The initial set of offspring is known as the first filial (F1) generation. The following generations mated at random until the population reached 10,000 mice. Table 1 shows data stratified between mice with and without the NF1 mutation. The variables analyzed include the number of mice with neurofibromas and the number of mice with MPNSTs.
Table 1 Number of cases of neurofibromas and MPNSTs in mice with or without an NF1 mutation
Experiment 2
Researchers created novel mouse models harboring a common nonsense mutation (exon 18 c.2041C>T; p.Arg681*) in addition to mouse models harboring a null allele due to exon 4 deletion (Δ4). To assess neurofibromin function in these models, researchers isolated and expanded mouse embryonic fibroblasts (MEFs) from embryos carrying different allelic mutations, then performed Western blot analyses and assayed neurofibromin and phosphorylated ERK (pERK) levels. The results are shown in Figures 1 and 2.
Figure 1 Western blot analyses for wildtype mice and mice harboring mutations
Figure 2 Expression of neurofibromin and pERK in wildtype mice and mice harboring mutations
Figures 1 and 2 from Kairong Li et al. June 2016. Disease Models and Mechanisms 9(7):dmm.025783
If two mice from the F1 generation of Experiment 1 were crossed, what percentage of their offspring would have neurofibromatosis?
Choose 1 answer: