PBL

Question 1

What is endochondral ossification?

Answer 1

The replacement of a cartilage model by bone.

Question 2

What causes mesoderm to differentiate into mesechyme?

Answer 2

The apical ectoderm ridge (AER) - this induces proliferation and differentiation of mesenchyme.

Question 3

Which part of the mesoderm gives rise to the mesenchyme involved in endochondral ossification?

Answer 3

Somatic lateral plate mesoderm.

Question 4

What are the three stages of signal transduction?

Answer 4

1. Detect
2. Transduce
3. Respond

Question 5

How do intracellular receptors affect a response?

Answer 5

• hydrophobic molecule passes into cell via plasma membrane
• then binds to sepcific intracellular receptor
• ligand-receptor complex can pass into nucleus and alter gene transcription/protein synthesis

Question 6

What is an example of a molecule which uses intracellular receptors?

Answer 6

Steroid hormones e.g. oestrogen and testosterone

Question 7

How does ion gated channels work?

Answer 7

• may be voltage gated or ligand gated
• either mebrane potential of binding of ligand will ‘open’ the gate
• this creates a channel through which ions can flow into the cell

Question 8

What is an example of a molecule which uses an ion gated channel?

Answer 8

Glutamate neurotransmitter

Question 9

How does a G protein coupled receptor work?

Answer 9

• ligand binds to receptor (extracellular)
• G protein binds to receptor (intracellular)
• G protein activates enzyme
• ezyme carries signal further into the cell

Question 10

Give an example of a molecule which uses a G protein coupled receptor.

Answer 10

Adrenaline

Question 11

How do enzyme linked receptors work?

Answer 11

• ligand binds to receptor (extracellular)
• intracellular region of receptor has enzymatic activity or is associated with an enzyme
• once activated by ligand the enzyme triggers a response

Question 12

What are a key subtype of enzyme linked receptors?

Answer 12

Tyrosine kinase receptors

Question 13

Give an example of a molecule which will use an enzyme linked receptor.

Answer 13

Many growth factors

Question 14

List the different types of cell receptors.

Answer 14

• intracellular
• ion gated
• G protein coupled
• enzyme linked

Question 15

What are the 2 main methods for signals to be transduced/amplified?

Answer 15

1. Enzyme cascades e.g. MAP kinase cascade follows on from many growth factors
2. Second messengers e.g. cAMP

Question 16

What is an oncogene?

Answer 16

A gene whose product is involved in inducing cancer. Most oncogenes are mutated forms of normal genes (proto-oncogenes) involved in the control of cell growth or division.

Question 17

Explain how a mutation can cause pituitary and thyroid adenomas.

Answer 17

• somatic point mutation of R201 or Q227 inhibits GTP hydrolysis
• constitutive activity mimics signal from hormones that stimulate proliferation and secretion in these glands

Question 18

How would a deletion/point mutation affect a protein?

Answer 18

Hyperactive protein made in normal amounts e.g. FGFR3 glycine replaced by arginine

Question 19

How does a regulatory mutation affect proteins?

Answer 19

Normal protein greatly overproduced

Question 20

How does gene amplification impact a protein?

Answer 20

Normal protein greatly overproduced

Question 21

How does chromosome rearrangement affect the protein?

Answer 21

• nearby regulatory DNA sequence causes normal protein to be overproduced
• fusion to actively transcribed gene produces hyperactive fusion protein

Question 22

What is achondroplasia?

Answer 22

A commonly encountered form of exteme short stature where poor bone growth results in shortened limbs.

Question 23

List some characteristics of achondroplasia.

Answer 23

• near normal trunk length with shorted arms and legs
• large head with prominent forehead and flattened bridge of nose
• increased curvtature of lower spine (lumbar lordosis)
• bowing of lower legs
• possible crowded teeth
• short, broad feet and hands with separation between middle and ring finger
• exceptionally flexible joints
• babies motor and mobility skils may develop more slowly but ultimately development is within normal range

Question 24

What is the inheritance pattern of achondroplasia?

Answer 24

• 80% are de novo ie not inherited from parents

- 20% are autosomal dominant

Question 25

What is the normal mode of action for FGFR3?

Answer 25

Ligand activated FGFR3 receptors can stimulate the growth of many cell types e.g. fibroblast but can also inhibit the growth of matrix producing chondrocytes in the growth plates via cell cycle inhibition.

Question 26

Describe the features of autosomal dominant inheritance.

Answer 26

• the trait appears in every generation
• each person with the trait has an affected parent
• when a branch of the family does not express the trait the trait fails to reappear in future generations
• males and females are affected roughly in equal numbers
• all persons without the trait are homozygous recessive e.g. aa
• all persons with the trait are homozygous domininant (AA) or heterozygous (Aa)

Question 27

How does a mutation in FGR3 result in achondroplasia?

Answer 27

• point mutation changes glycine to arginine
• mutant amino acid side chain gives rise to a small increase in active receptors
• therefore more inhibition of chondrocytes
• therefore less bone growth