Protein expression: RbAp48 and age-related memory loss

The retinoblastoma-associated protein 48 (RbAp48) is a 48-kDa protein that was initially characterized by its ability to bind to the retinoblastoma protein Rb. RbAp48 is present in protein complexes that control histone acetylation and remodel chromatin, such as the nucleosome remodeling and deacetylase (NuRD) complex, the switch-independent 3 (SIN3)/histone deacetylase (HDAC) complex, and the CAF-1 complex, a chromatin assembly factor. Changes in RbAp48 expression have been linked to age-related memory loss in both humans and wild-type mice. The following studies were performed to assess the role of RbAp48 in age-related changes in the hippocampus, a region of the brain that plays an important role in memory and information consolidation.

Experiment 1

Scientists investigated the expression of RbAp48 in two different regions of the hippocampus, known as the dentate gyrus (DG) and the entorhinal cortex (EC); they compared the expression level of RbAp48 in each region with age. The results are shown in Figure 1.

Figure 1 RbAp48 expression in the dentate gyrus (DG) or entorhinal cortex (EC) versus age

Experiment 2

Researchers compared wild-type mice and mice expressing an inactive form of RbAp48, known as dominant-negative mice (RbAp48-DN). Groups of mice were tested for hippocampal-dependent dysfunction with an object recognition test. In this test, the mice were exposed to two objects and were given time to learn and explore them (“training” time). After 24 hours, the mice were returned to the objects but this time one of the original objects was replaced with a novel object. After 48 hours, the mice were returned again and exposed to the same original object that was there in the 24-hour test, but the second object was yet another novel object. The results of these tests were measured by a discrimination index defined by Equation 1, where object A is the novel object in the 24- and 48-hour tests.

Equation 1 Discrimination index

The researchers first compared young wild-type mice with young RbAp48-DN mice. The results are shown in Figure 2.

Figure 2 Discrimination index outcomes in young wild-type vs RbAp48-DN mice

The researchers then performed the same comparison on young and old wild-type mice.

Figure 3 Discrimination index outcomes in young and old wild-type mice

DN mice contain one normal copy of the RbAp48 gene. Which of the following best describes their phenotype?

(Choice A)
The mutated allele produces a protein with enhanced or constitutive activity, leading to a gain-of-function phenotype that dominates over the normal allele's function.
(Choice B)
The mutated allele produces a non-functional protein that prevents the normal protein from functioning properly in a heterozygous individual.
(Choice C)
Defects in the expression of the mutant allele also inhibit the expression of their normal allele in a heterozygous individual.
(Choice D)
The mutated allele performs a function that counters the activity of the normal allele, leading to overall inactivity.

MCAT

Course: MCAT > Unit 2

Problem