Muscular Dystrophies

Question 1

Describe the impact of muscle disintegrity on the body.

Answer 1

Muscle disintegrity leads to muscle wasting diseases known as myopathies.

Question 2

Do myopathies primarily affect the musculature?

Answer 2

Yes, myopathies primarily affect the musculature.

Question 3

Define myopathies.

Answer 3

Myopathies are genetic disorders that tend to affect the connection between the sarcomeric structure and the basement membrane surrounding muscle cells.

Question 4

How many genes are likely to result in myies?

Answer 4

More than 100 genes are likely to result in myopathies, with around 40 genes identified so far.

Question 5

Describe the types of proteins involved in myopathies.

Answer 5

Proteins involved in myopathies include extracellular matrix proteins, transmembrane proteins, membrane-associated proteins, cytoplasmic proteases, cytoplasmic proteins associated with sarcomeres, protein modifying enzymes, and nuclear membrane proteins.

Question 6

Describe the classification of myopathies related to congenital muscular dystrophies.

Answer 6

Clinical symptoms are detected after birth, including muscle weakness (e.g. floppiness, reduced spontaneous movement) and delayed motor milestones.

Question 7

Describe the classification of myopathies related to muscular dystrophies.

Answer 7

Clinical features range from mild to severe, with some cases being lethal.

Question 8

How many genes are likely to result in myies, and how many have been identified so far?

Answer 8

More than 100 genes are likely to result in myies, with approximately 40 genes identified.

Question 9

What types of proteins are involved in genes related to myopathies?

Answer 9

Extracellular matrix proteins, transmembrane proteins, membrane-associated proteins, cytoplasmic proteases, cytoplasmic proteins associated with sarcomeres, protein modifying enzymes, and nuclear membrane proteins.

Question 10

Describe the components involved in extracellular matrix-cytoskeleton interaction according to the provided content.

Answer 10

Components include α DYSTROGLYCAN, β DYSTROGLYCAN, INTEGRIN α7β1, SARCOGLYCAN, DYSTROPHIN.

Question 11

What are some basement membrane components mentioned in the content?

Answer 11

Nidogen, Laminin, Collagen IV, Perlecan are mentioned as basement membrane components.

Question 12

the term ‘DYSTROGLYCAN’ based on the content.

Answer 12

DYSTROGLYCAN is a protein involved in extracellular matrix-cytoskeleton interaction.

Question 13

How are the components α DYSTROGLYCAN and β DYSTROGLYCAN related in the context of the content?

Answer 13

They are both involved in extracellular matrix-cytoskeleton interaction.

Question 14

What is the significance of LAMININ in the provided content?

Answer 14

LAMININ is a component of the basement membrane mentioned in the content.

Question 15

Do the components mentioned play a role in the interaction between extracellular matrix and cytoskeleton?

Answer 15

Yes, the components mentioned are involved in extracellular matrix-cytoskeleton interaction.

Question 16

Describe the laminin isoforms present in skeletal muscle.

Answer 16

Two laminin isoforms in skeletal muscle contain the α2, β1 or β2, the γ1, and the α2 chains.

Question 17

What are the consequences of a deficiency in the laminin α2 chain in congenital muscular dystrophy?

Answer 17

Primary deficiency leads to CMD in 50% of patients, with increased α4 and moderately increased α5 chains.

Question 18

How does partial deficiency of the laminin α2 chain differ from primary deficiency in congenital muscular dystrophy?

Answer 18

Partial deficiency is associated with milder CMD forms and the mutated chain may retain some functions.

Question 19

Define the mechanisms explaining laminin α2 CMD.

Answer 19

Perturbed receptor/ligand interaction, inability to bind to dystroglycan, weak binding to integrins, and impaired self-polymerization.

Question 20

What are the additional laminin chains present during skeletal muscle development besides the adult chains?

Answer 20

During development, α4 and α5 chains are also present in addition to the adult chains.

Question 21

What is the impact of in-frame deletions in the N-terminal part of the laminin α2 chain?

Answer 21

These deletions allow binding to dystroglycan and integrins but impair the ability to self-polymerize.

Question 22

Describe the Dystrophin-Glycoprotein ComplexDGC)

Answer 22

A multiprotein complex composed of dystroglycan, sarcoglycan, sarcospan located in the plasma membrane (sarcolemma), binding to laminin on the outside of the muscle cell and dystrophin on the of the cell.

Question 23

What is the role of Dystroglycan in the DGC?

Answer 23

Dystroglycan is post-translationally cleaved into a-dystroglycan that binds to laminin and b-dystroglycan that mediates binding to dystrophin.

Question 24

Define Dystroglycan

Answer 24

Dystroglycan is a gene that is post-translationally cleaved into a-dystroglycan and b-dystroglycan, which interact with each other and are involved in positioning the sarcoglycan complex to the DGC.

Question 25

How is Dystroglycan involved in muscular dystrophies?

Answer 25

Dystroglycan, due to its central position in the DGC, is a candidate gene involved in muscular dystrophies, although no mutations in dystroglycan have been identified in humans yet.

Question 26

Describe the structure of a-dystroglycan.

Answer 26

a-dystroglycan has a dumbbell shape with heavily glycosylated rod-like domains that mediate binding to laminin.

Question 27

What happens in some forms ofital muscular dystrophy related to a-dystroglycan modification?

Answer 27

In some forms, a-dystroglycan is hypoglycosylated due to a primary defect in protein-modifying enzymes of the Golgi apparatus and endoplasmic reticulum, leading to its inability to bind to the extracellular matrix ligand laminin.

Question 28

Explain the consequence of hypoglycosylated a-dystroglycan in muscle fibers.

Answer 28

Hypoglycosylated a-dystroglycan leads to the loss of connection between the extracellular matrix and cytoskeleton, resulting in the instability of muscle fibers.

Question 29

What are the components of the transmembrane complexes of the sarcolemma involving dystroglycans?

Answer 29

The components include α-dystroglycan, β-dystroglycan, integrin α7β1, sarcoglycan, dystrophin, and the basement membrane.

Question 30

How is a-dystroglycan modified according to Campbell, 1995 and Worton, 1995?

Answer 30

a-dystroglycan is modified according to Campbell, 1995 and Worton, 1995 in the context of the connection between the matrix and cytoskeleton.

Question 31

Describe integrins.

Answer 31

Integrins are heterodimeric proteins composed of an alpha and a beta chain that bind to their ligand on the outside of the cell.

Question 32

What is the main expression site of Integrin a7b1?

Answer 32

Mainly expressed in skeletal and cardiac muscle.

Question 33

What is the specific function of Integrin a7b1 as a laminin receptor?

Answer 33

It can connect the extracellular environment to the cytoskeleton.

Question 34

What are the consequences of Integrin a7b1 deficiency in mice through gene targeting?

Answer 34

Leads to a specific form of progressive muscular dystrophy.

Question 35

How does Integrin a7b1 deficiency manifest in humans due to out-of-reading frame mutations?

Answer 35

Leads to a mild form of congenital muscular dystrophy, with only three identified cases so far.

Question 36

Describe Duchenne Muscular Dystrophy.

Answer 36

Duchenne Muscular Dystrophy is the most common form of muscularrophy in humans, affecting about 1 in 3000 boys. It is caused by dystroph deficiency.

Question 37

What is the difference between Becker Muscular Dystrophy and Duchennecular Dystrophy

Answer 37

Becker Muscular Dystrophy is a milder caused by small in-frame deletions that partially maintain protein function, while Duchenne Muscular Dystrophy is a severe form due to the complete absence of the protein.

Question 38

How do mutations leading to Duchenne Muscular Dystrophy occur?

Answer 38

Mutations causing Duchenne Muscular Dystrophy can be inherited or occur spontaneously due to the large size of the gene.

Question 39

Define Dystrophin.

Answer 39

Dystrophin is a protein whose deficiency leads to muscular dystrophies, particularly Duchenne Muscular Dystrophy.

Question 40

What is the role of the mouse model mdx in research on Duchenne Muscular Dystrophy?

Answer 40

The mouse model mdx is used in extensive studies for potential gene therapy for Duchenne Muscular Dystrophy.

Question 41

Describe the clinical phenotype of muscular dystrophies.

Answer 41

The clinical phenotype of all muscular dystrophies is similar, but the molecular mechanisms leading to the diseases may differ.

Question 42

What is the importance of animal models in studying muscular dystrophies?

Answer 42

Animal models are useful tools to gain insight into disease mechanisms and test therapeutic strategies for muscular dystrophies.

Question 43

Explain the significance of Integrins in skeletal muscle.

Answer 43

Integrins are discussed as potentially important players in skeletal muscle function in the context of muscular dystrophies.

Question 44

What is the suggested reading related to the dystrophin-glycoprotein complex?

Answer 44

The suggested reading includes ‘The dystrophin-glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies’ by Rando T.A. (2001).

Question 45

Describe the defect in the laminin a2 chain expressed by dystrophic dy mice.

Answer 45

The laminin a2 chain expressed by dystrophic dy mice is defective in its ability to form polymers, as discussed in the literature.

Question 46

What is the focus of the study by Guo et al. (2003) regarding laminin a2 deficiency?

Answer 46

Guo et al. (2003) focus on genotype-phenotype correlation in mutant mice with laminin a2 deficiency and muscular dystrophy.

Question 47

Define Dystroglycan.

Answer 47

Dystroglycan is a protein involved in muscular dystrophies, particularly in the context of pathogenesis of human disease.

Question 48

What is the content of Vander’s Human Physiology Chapter 9 related to?

Answer 48

Vander’s Human Physiology Chapter 9 provides general muscle knowledge and insight into Duchenne muscular dystrophy.

Question 49

Do the laminins play a role in muscle development and muscular dystrophies?

Answer 49

Yes, laminins are involved in muscle development and are relevant in the context of muscular dystrophies.

Question 50

Describe the role of Dystroglycan in the context of muscular dystrophies.

Answer 50

Dystroglycan is discussed in the content as a relevant protein in the pathogenesis of human muscular dystrophies.

Question 51

What is the focus of Mayer U.’s study (2003) regarding Integrins in skeletal muscle?

Answer 51

Mayer U.’s study (2003) questions whether Integrins are redundant or important players in skeletal muscle.

Question 52

Explain the importance of animal models in understanding disease mechanisms and testing therapies for muscular dystrophies.

Answer 52

Animal models are crucial tools for gaining insight into disease mechanisms and evaluating potential therapeutic strategies for muscular dystrophies.

Question 53

Describe the conclusion drawn regarding the molecular mechanisms of muscular dystrophies.

Answer 53

While the clinical phenotype of muscular dystrophies is similar, the molecular mechanisms leading to the diseases are likely to differ, as discussed in the content.

Question 54

What is the potential of gene therapy in treating Duchenne Muscular Dystrophy?

Answer 54

Extensive studies are being conducted for potential gene therapy for Duchenne Muscular Dystrophy.

Question 55

How does the severity of Duchenne Muscular Dystrophy compare to Becker Muscular Dystrophy?

Answer 55

Duchenne Muscular Dystrophy is more severe than Becker Muscular Dystrophy, with patients usually becoming wheelchair-bound by age 10 and dying post-puberty.