Pigment Flashcards
In which tissues are melanocytes found?
Skin, oral mucosa, eye, leptomeninges, and ear
Melanoblasts come from which embryonic structure?
Neural crest
A mutation in which gene commonly causes piebaldism on the forehead, chest, abdomen and limbs in both people and animals?
KIT
A mutation of which gene is associated with white belting in cattle?
TWIST2
Interactions between KIT/KIT ligand (SCF) on which cells controls migration of activated melanocytes from the stem cell pool to the anagen hair bulb to pigment each new hair shaft?
Melanocytes (KIT) and keratinocytes (KIT ligand/SCF)
Grey horses have a mutation in which gene?
STX17
What percentage of grey horses develop melanomas by 15 years old?
70-80%
What colours are eumelanin and pheomelanin?
Black-brown and yellow-red
What are the four stages of melanosome formation?
- establishes the organelle vesicular structure
- adds internal protein fibrils (premelanosome protein 17 (PMEL), also called Silver (SILV)) that hold melanin and give the ellipsoid melanosome shape
- melanosomes, melanin deposits along, and thickens, luminal fibrils, which are still visible ultrastructurally
- melanin deposition obscures fibrils completely
What signs occur with grey collie syndrome?
Cyclical neutropaenia, thrombocytopaenia, anaemia
Dilute skin and hair colour
Grey/pale tan nasal planum
Recurrent infections
What causes colour dilution in grey collie syndrome?
Dilution is due to decreased melanisation of melanosomes due to failure of complete delivery of melanin synthesis enzymes to the melanosome.
Chediak-Higashi syndrome has been reported in which breed of cats?
Persians
Chediak-Higashi syndrome has been reported in which breeds of cattle?
Hereford, Brangus and Japanese Black
Mutations in which gene cause merle coat colours?
SILV (silver protein; premelanosome protein 17)
Leopard spotting complex in many horse breeds is associated with a mutation in TRPM1; what other clinical sign accompanies it?
Congenital stationary night blindness
Leopard spotting patterns in horses are associated with TRPM1 and which other gene mutations?
RFWD3 at the PATN1 locus that extends areas of white in the pattern
An essential cofactor for tyrosinase, dietary deficiency of which mineral leads to greying of the coat?
Copper
Define poliosis
Premature greying of hair
Define achromotrichia
Loss or absence of hair pigment
Where on the body are lentignes typically seen in dogs?
Ventrum
Where on the body are lentignes typically seen in cats?
Lips, nose, gingivae and eyelids
What mechanism leads to dark points in colour point cats?
Temperature sensitive hair bulb tyrosinase that is inactivated at 35-37^C
Which breeds of dog are prone to post-inflammatory melanotrichia?
Yorkies, Silkies, Bedlingtons, OES and Poodles
Are melanocytes present in albinism?
Yes, melanocytes are present but a mutation in the tyrosinase gene leads to a lack of tyorsinase needed for melanin synthesis
What is the phenotype of Waardenburg-Klein syndrome?
Amelanotic skin and hair, deafness and blue or heterochromic irides
In dogs, one melanocyte makes contact with approximately how many keratinocytes?
20-36
Alpha-melanocyte stimulating hormone promotes synthesis of which type of melanin?
Eumelanin
Agouti signal protein promotes synthesis of which type of melanin?
Pheomelanin
Where does melanogenesis occur?
In melanosomes
Which gene, other than KIT, is associated with white spotting in cattle?
MITF
Brown Swiss cattle, Holstein and Simmental cattle
Roan/Blue coat patterning in cattle is associated with which gene?
KITLG (KIT ligand/SCF)
Mutations in KITLG (SCF) contribute with other genes, likely MC1R and others, to increased incidence of which neoplastic process?
Digital squamous cell carcinomas in large black dogs, like the Standard poodle
In dogs, mutations of which genes are associated with Waardenberg syndrome?
MITF
SILV (silver protein; premelanosome protein 17)
In horses, mutations of which genes are associated with Waardenberg syndrome?
EDNRB, PAX3, and/or MITF
In cats, a mutation of which gene is associated with Waardenberg syndrome?
KIT
Lethal white foal syndrome, with white hair coat, hypopigmented blue eyes, congenital sensorineural deafness and colonic aganglionosis, is associated with a mutation of which gene?
EDNRB
Same mutation in lethal white lamb syndrome
In pigmentation of hair, keratinocytes produce ____ to activate KIT on melanocytes
SCF (kit ligand)
Which stages of melanosome formation do not involve melanin?
1 and 2
A mutation in which gene is associated with grey collie syndrome (canine cyclical hematopoiesis)?
AP3B1
What is unusual about the appearance of neutrophils in Chediak-Higashi syndrome?
They contain giant intracytoplasmic organelles that are visible as large granules (pathognomonic)
Oculocutaneous albinism with nystagmus is seen in which breed of cat?
Siamese
‘White’ (cream) dobermans, with a mutation in SLC45A2, are at increased risk of which type of neoplasia?
Melanoma
Deficiency of which dietary amino acids leads to decreased melanin synthesis and changes coat colour?
Phenylalanine (Phe) and tyrosine (Tyr)
Lavender foal syndrome (LFS, also called coat color dilution lethal) in Arabian horses, characterized by dilute coat color and multiple neurological signs in new born foals, is due to a mutation in which gene?
MYO5A
Myosin5a facilitates the transfer of melanosomes to the keratinocytes AND is also expressed in the nervous system
Diluted coat color associated with mutations in _____ is reported in several species and examples are in cats, dogs and cattle
MLPH
Which gene/factor is important for melanoblast survival and regulation of the trancription of pigment related genes?
MITF (micropthalmia transcription factor)
Which gene/factor is important for embryonic melanoblast survival, migration and differentiation?
KIT
Which gene/factor is important for early embryonic melanoblast migration and population expansion?
EDNRB (endothelin receptor B)
Which factors are important for differentiation of neural crest cells to melanocytes?
SOX10, FOXD3, PAX3, MITF, KIT, EDNRB, FGF, WNT, P-cadherin, and E-cadherin
Apart from melanocytes, which cells express c-KIT?
Mast cells
Hematopoetic cells
Interstitial cells of Cajal
Gonadal germ cells
White spotting in Northern Finn cattle and Swedish Mountain cattle is associated with which other abnormality and which gene mutation?
Gonadal hypoplasia (LHS) KIT, BTA29 chromosomal duplication-translocation
What is the role of SILV / PMEL17 in melanosome formation?
It adds internal protein fibrils (also called premelanosome protein 17 (PMEL)
Apart from KIT/KIT ligand interactions between melanocytes and keratinocytes, which other factors important for melanocyte stem cell interactions in the hair follicle?
WNT, B-RAF C-RAF, NOTCH, TGF-B, EDN, and NFIB
What do organelle cargo sorting complexes do in melanogenesis?
They shuttle proteins from the golgi complex to the developing melanosome
Name the protein complexes involved in cargo sorting in melanogenesis
BLOC-1, BLOC2, BLOC-3 or Adaptor Protein Complex-3 (AP-3)
A mutation in which gene causes equine multiple congenital ocular anomalies in silver and silver dapple horses?
SILV
What is the pigmentary synapse?
Melanosome transfer at dendrites of melanocytes to keratinocytes
How many keratinocytes does one melanocyte transfer melanosomes to in the follicular melanin unit?
5
Which proteins, at the melanocyte dendrite tip, facilitate transfer of melanosomes to keratinocytes?
Rab27a, melanophilin (MLPH), myosin-5a
Which diseases in animals are associated with mutations in genes encoding proteins involved in melanosome transfer?
Lavender foal syndrome (MYO5a)
Colour dilution alopecia (MLPH)
Which disease in dogs is associated with a mutation in the gene involved in cargo sorting complexes?
grey collie syndrome (canine cyclical hematopoiesis) = AP3B1
Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by extensive hypopigmentation of hair, skin and eyes as well as a silvery sheen to the hair. It has been linked to mutations in CHS1 (also called lysosomal trafficking regulator (LYST)), which codes for the CHS-1 protein - what does CHS-1 do?
It affects vesicle membrane fission/fusion events; this affects multiple lysosomes and lysosome related organelles, in addition to melanosomes in different cell types in the body
(hence the large intracytoplasmic organelles seen in neutrophils!)
The delayed tanning pathway occurs as UVB produces keratinocyte DNA damage, causing p53-mediated expression of the pro-opiomelanocortin (POMC) gene that is processed to release ________ which stimulates the melanocortin 1 receptor (MC1R) on melanocytes, leading to m-MITF expression and melanogenesis
α-melanocyte stimulating hormone (α-MSH)
MC1-R predominates in melanocytes and its agonists include ______ and ______, both cleavage products of pro-opiomelanocortin (POMC)
alpha-melanocyte stimulating hormone (α-MSH) Adrenocorticotropic hormone (ACTH)
Name the MC1-R antagonist
Agouti signal protein - stimulates pheomelanogenesis
