Aufgabe 3 - Teilaufgabe 2 · Abitur NRW Biologie GK · Haupttermin · bilingual Englisch 2022

Material A: Ivermectin

Dogs can be infested with parasites, for example lice, mites or ticks. Substances such as ivermectin are used to fight these parasites. Ivermectin is a neurotoxin which is lethal particularly to invertebrates. It binds to glutamate-gated chloride ion channels in the postsynaptic membrane and opens them permanently. Glutamate-gated chloride ion channels are found only in invertebrates.

Ivermectin is less toxic to vertebrates and thus is used to treat dogs with parasitic infestations. Ivermectin is a fat-soluble substance, which can diffuse through the cell membrane. In animals treated with ivermectin, it accumulates in their livers and fat tissues and is slowly released from there. The substance then circulates in low amounts in the blood of the treated animals and is taken up by the parasites.

Material B: Ivermectin Sensitivity

In higher concentrations, ivermectin can also bind to GABA-gated chloride channels in vertebrates and activate them. This can cause neurotoxic effects, especially in the central nervous system of vertebrates.

After a treatment with ivermectin, symptoms such as movement disorders, cramps, lightheadedness 1 and even coma could often be observed in collies and other dog breeds. Since not all dogs of a breed are affected by ivermectin in the same way, the individual causes for this sensitivity were analysed.

A mutation in the MDR1 gene was identified as the cause of this sensitivity. Experiments with mice were carried out to understand the function of MDR1 in mammals. Researchers used wild-type mice and genetically modified mice whose MDR1 gene had been inactivated. After the treatment with ivermectin, its concentration in different tissues was measured in both groups (Table 1).

In mammals, the MDR1 gene codes for the transport protein MDR1. It uses ATP to transport foreign substances 2 out of the cells and back into the bloodstream, so that they can be removed. MDR1 also occurs in the cells of the blood vessel walls of the blood brain barrier. The blood brain barrier is selective and allows only certain substances from the blood to enter the brain. Thus, it creates a barrier between the central nervous system and the blood.

1 Benommenheit

2 hier: körperfremde Stoffe

Material C: MDR1 Mutations in Collies

The results of genetic analyses of the MDR1 gene in collies which are sensitive to ivermectin are shown in Table 2. The whole MDR1 protein is 1281 amino acids long.

Material D: Detection of the MDR1 Alleles

The mode of inheritance of ivermectin sensitivity is autosomal recessive. DNA samples of different dogs were analysed using polymerase chain reaction (PCR). The respective primer pairs as well as the expected sizes of the amplified fragments are shown in Figure 1. The results of a gel electrophoresis of the PCR products are shown in Figure 2.

Material E: Diagram and Codon Table of the Genetic Code

2. Compare how ivermectin is distributed across various mouse tissues (Table 1) and deduce which function the MDR1 protein performs in mammals (Materials A and B). Work out the amino acid sequences encoded by the DNA sequences given in Table 2 and determine the type of mutation involved (Materials C and E). Illustrate how the MDR1 protein and the affected dogs are impacted (Materials A–C). [24 Punkte]

a)

b)

Determine the amino acid sequences of both alleles (triplets 73 to 81) in the 3-letter code (separated by hyphens, e.g. Gly-Asn-...) and identify the type of mutation:

c)