Mutations in the Intracellular Sensor Gene NOD2 Are Associated with Crohn's

question 2

Essay

Mutations in the intracellular sensor gene NOD2 are associated with Crohn's disease, a chronic severe inflammatory disease of the gastrointestinal tract. NOD2 is normally expressed in Paneth cells of the intestine, as well as in macrophages, monocytes and dendritic cells. To understand the effects of the NOD2 mutation, a line of knock-in mice was generated in which the wild-type NOD2 allele (NOD2^+/+) was replaced with a variant disease-associated allele that causes a frameshift mutation in the NOD2 protein coding sequence (NOD2^m/m). Isolated macrophages from wild-type mice were and those from NOD2^m/m mice were stimulated in vitro with the NOD2 ligand, muramyl dipeptide (MDP, a component of bacterial peptidoglycan), and inflammatory cytokines IL-6 and TNF- $\alpha$ were measured 3 hours later, as shown in Figure Q2)24). What is the most likely explanation for why this NOD2 mutation predisposes individuals to Crohn's disease?

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Definitions:

Self-Concept

An individual's perception of themselves, including beliefs, feelings, and thoughts about one's abilities, appearance, and values.

Cognitive Development

The process by which individuals acquire and develop the ability to think, understand, and reason over time.

Social Referencing

A baby’s adjustment of its reactions to objects or events based on feedback provided by a caregiver. For example, a baby may look at a caregiver’s facial expression before approaching a new toy.

Intergenerational Transmission

When parents repeat with their children the patterns of trauma, rejection, and maltreatment that they experienced as children from their own parents.