Function of Agouti and Extension Genes - about Receptors and Pigment Types

[reh]

• To create the alternating colored bands on Agouti hairs, the pigment cells need to switch between the production of black and yellow pigments during the hair growth. This change is called pigment type switching. It is also responsible for the creation of areas with just light or just dark colored hairs.
  
  
• The process is similar to that of a key lock, for example the ignition lock in a car. The melanocortin receptor 1 (MC1R) being the lock, the ubiquitous melanocyte-stimulating hormon (MSH) and the spatial/temporarily available agouti signal protein (ASIP) being keys.
  
  
• MSH is always present, whilst ASIP only becomes available during the growth of the yellow portion of the hair.
  
  
• MSH causes the the switch to signal. This signal induces the pigment-creating cells to produce black pigment. The key ASIP fits into the switch, but doesn't switch it on - so doing nothing but preventing the use of the MSH-key.
  
  
• A cell with working switch therefore produces black pigment in the presence of MSH. If ASIP becomes available temporarily, it replaces the MSH and turns off the signal. Thus the cells produces yellow pigment.
  
  
• The Extension series holds the construction plan for the key switch (MC1R), the Agouti series the construction plan for ASIP.
  MC1R-Mutations create switches which are either constantly active / overactive (steel) or defect (yellow). For ASIP a fault in the construction plan may interrupt the key production leading to nonfunctioning keys.
  
  
• A special case is the Japanese factor. It resembles the gene for steel/dominant black, yet it only acts in the dark areas of the coat. It is not active in the light parts, so there are no switches at all. Therefore the Japanese factor is actually recessive towards the nonextension gene in the light areas, whilst it is dominant towards the normal extension in the dark areas.

 

[reh]

There is much confusion about actual banding, tipping and so on.
If there is something questionable about a rabbit it is a good idea to pluck a bunch of hair, separate them in guardhair and downhair and put them on a white (or dark) sheet. Ideally then take a sharp photo.
This is much better then unsharp images of moving rabbits in bad light conditions .


There may be more then one agouti band looking into the fur funnel, but normally each single hair has only one agouti band. Much differences in color are due to different differences between length of guard and down hair causing more or fewer of the agouti band to influence the color appearance.

steeled chinchilla steel/dark grey
There is nothing like gold or silver tipped anything (hairs always start with dark pigment, silvered hairs have no pigment). If the receptor is overactive, do not letting the ASIP switch off the signaling the needed time, how should it cause the agouti band earlier then normal on the normally dark tip?


If you want me to believe otherwise prove it with an hair image ;-)

By the way, the agouti band sits on the thickest part of the hair below the hair tip. There may be a connection between hair growth rate and pigment switching. Hairs with doubled agouti bands caused by x-ray treatment experiments had not only double bands but also double granne/bristle or how its called in english.

Steel colors have no light tipping at all, but a very narrow agouti band.
Silvers have hairs lacking pigment producing melanocytes, the thin white hairshaft may disappear inbetween all the colored down hair.
White under color occurs if pigment cells cease producing pigments.

 

[reh]

You may add some temperature sensitivity to the color confusion regarding the nonextension receptor, which would explain the dark points similar to this in himalaya in nonagouti yellow (no, there is no connection with ch beside the skin temperature).
Satinangora Rex

 

[judymac]

White under color occurs if pigment cells cease producing pigments

Do you know what causes the cells to cease production of pigment?

 

[Alaska Satin]

There is much confusion about actual banding, tipping and so on.
If there is something questionable about a rabbit it is a good idea to pluck a bunch of hair, separate them in guardhair and downhair and put them on a white (or dark) sheet. Ideally then take a sharp photo.
This is much better then unsharp images of moving rabbits in bad light conditions .


There may be more then one agouti band looking into the fur funnel, but normally each single hair has only one agouti band. Much differences in color are due to different differences between length of guard and down hair causing more or fewer of the agouti band to influence the color appearance.

This is my friend's English Angora. I don't think the numerous bands are a result of new + old coats.

 

[judymac]

I agree that this can be confusing. Here is an English Angora rabbit. In the back, you can see the full coat. To the right, the outer coat has been removed, leaving the intermediate coat. At the bottom you can see a third coat emerging from the skin. While it looks like there are three separate agouti bands, it's really three different layers of hair, each with one set of banding. I'm not saying you can't ever get multiple bands, just that in my herd, the multiple banding is an artifact of the multiple coats.

For those with single-coated rabbits, putting the individual hairs on the paper would show the difference, what a good idea. I would never have thought of separating the guard hairs, they really do look very different. Fascinating. I don't raise steel, but when I get some fiber, I will definitely try the white paper trick. Should be an interesting experiment.

 

[reh]

There are only two colors. Ok, two and a half. They are formed in little granules called melanosomes.

• Dark pigment called eumelanin (black)
• Light pigment called pheomelanin (yellow-red)
  If no pheomelanin can be made due to albino mutations, melanosomes stay (mostly) empty, colorless, blank
• if one distinct part needed to make eumelanin is missed, it cannot fully develop into its black form - it stays dark brown (the half one - similar to light burnt black)
• Blue is not a color, its a structure which causes black eumelanin looking blueish by light scattering.
  Dilution is a melanosome transport malfunction - melanosomes are not evenly distributed through the hair shaft but stored in in uneven patches/clumps (look at hairs using a microscope) .
• White is no color, literally

Hair is growing from the tip, not vice versa, so look at color bands from the tip too.
No matter if normal, rex or angora hair, in agouti there is a dark tip, a yellow/light pheomelanic band and the remaining part of the hair stays eumelanic.
The time when ASIP is working may differ a little. It may be narrowed (steel ES) or elongated (wideband ww).

• Timing of ASIP is causing yellow/white hair color and is causal for hair banding / body zoning.
• This is not influenced by base colors (black, brown, dilute), albino mutations or the amount/depth of yellow pigment).

In angoras hair do grow for a longer time, so the biggest part of the hair is dark on colors with normal extension E.
In rex hairs are twisted, therefore shorter and no/few difference in length of hair types.
As melanosome production slows down this pigment granules become fewer, bigger, more uneven distributed further down the hair shaft - you get it - similar situation like in diluted rabbits.
Diluted hairs may have a little blank tip - due to the transport problem eumelanosomes may not be in place at time.


diluted / nondiluted
Bottom part of hair

 

[reh]

Agouti markings​

What exactly is this? Breed descriptions describe a lot of things like middle band, light eye rings, nose, ear, jaw, belly, lap spots, ....
Regarding the action of ASIP this has not much to do with yellow/red coloration. Agouti causes the parts without eumelanin. Actually there is no difference between agouti banded back hair and all this lighter parts. They all consist of the noneumelanic agoutiband caused by ASIP.

Agouti
Chinchilla
Wideband Agouti

As you see, the red color lightens up from back to belly, the agouti band gets wider and the dark tips narrowing up to disappearance. Its the same for eye rings, nape of neck and so on - no dark tips there.

There are two different forms of the transcript which carries the ASIP blueprint from the cell core to the protein machinery. Bot result in the same ASIP produced, but may differ in if and how often this blueprint is used. One of them occures a lot more on back then on belly, the other one is active on belly/the light parts only.

Other then the ubiquitous MSH, ASIP is made in the hair papilla only. This allows all this colorations like in leopard, chipmunk, giraffe, zebra, ... to develop in the right place.

Color differences between summer and winter fur can be explained by various length differences between guard hair and down hair. The coat may look lighter or darker, depending on how much of the guard hairs agouti band is hidden by the down hair.

Btw., the length of dark tip + agouti band stays nearly the same, but belly fur is shorter, so narrower undercolor.
(I am not sure regarding this in steels, which show an agouti band in second guard hair, but not in downhair.)

 

[reh]

Yellow/Red Coloration​

The intensity of pheomelanic color seems to be independent of agouti, there are distinct parts prone to more reddish color:

• top of head
• dorsal stripe, nape of neck
• top of tights, crescent-shaped
• heels
• lap spots

Like in rusty back on chinchilla



For yellow/red pheomelanin cystein is needed. If cystein is available, pheomelanin is made first, which will be covered later with dark pigment in eumelanosomes. PH is also important.

• lots of active tyrosinase + few cystein = dark eumelanin
• few active tyrosinase + lots of cystein + more acidic milieu = yellow/red pheomelanin

As long as melanocytes are running the "yellow" program several genes including TYRP (brown) are not working.

In case someone wonders how yellow color intensity may be changed:

• Subtile grey, Sut (SLC7A11) in mice represents a cystin transporter located in melanocyte membranes.
• Another one (MFSD12) transports cystein into melanosomes.
• Ionen transporter (changing PH)
• a lot more not yet understand things.

Btw., lap spots are counted as agouti markings - look at your tortoise rabbits to check it yourself ;-)

 

[judymac]

In case someone wonders how yellow color intensity may be changed:

Thank you for this explanation. And yes, I wondered. When you read human hair color studies, they suggest the reason we have so many different hair colors is because the hairshaft is colored with a blend of pigments. I've read a number of technical journal articles on this, but I think Wikipedia sums it up in a way much more readily understood:

"Eumelanin, which has two subtypes of black or brown, determines the darkness of the hair color;[4] more black eumelanin leads to blacker hair, and more brown eumelanin to browner hair.[6] All human hair has some amount of both pigments.[9] Over 95% of melanin content in black and brown hair is eumelanin.[9] Pheomelanin is generally found in elevated concentrations in blond and red hair,[4] representing about one-third of total melanin content.[9] If there is no black eumelanin, the result is strawberry blond.[6] Blond hair results from small amounts of brown eumelanin with no black eumelanin.[6]"​

I realize that genetics between species doesn't necessarily carry over. Obviously people are self-colored, non-agouti. So the whole agouti shift between the black/brown eumelanin and the yellow/red pheomelanin isn't part of the human hair equation. But I still wonder how the rufus modifiers change the yellow into red. A high rufus self chocolate looks very different than a regular chocolate. How does it do that? Do our self rabbits have a blend of melanins?

If you are breeding rabbits to the Standard of Perfection, it doesn't really matter how it works, you just follow the breeding guidelines, and keep the rabbits that match the standard. After generations of always matching the standard, you'll have a line that is fairly reliable in the necessary genetics (whatever they are) to make that color properly. You simply keep the rabbits that match the standard and breed them together, and then keep the best of the next generation.

But I'm a curious sort, I like to know 'why' it works. Guess that's what fuels all these scientific studies, when you get a question, you try to find a way to answer it.

 

[seashore]

Obviously people are self-colored, non-agouti.

Our species missed out. We need agouti-haired humans, and harlequin

Seriously though, thank you both. This is extremely interesting!!
I, also being a curious sort, am now going down the rabbit hole of human hair genetics...

 

[mrscllc]

Our species missed out. We need agouti-haired humans, and harlequin

Seriously though, thank you both. This is extremely interesting!!

Hah, I think people are trying to recreate this in hair salons now too!

 

[mrscllc]

Yellow/Red Coloration​

The intensity of pheomelanic color seems to be independent of agouti, there are distinct parts prone to more reddish color:

• top of head
• dorsal stripe, nape of neck
• top of tights, crescent-shaped
• heels
• lap spots

Like in rusty back on chinchilla.

So this reddish cast on a chinchilla is resulting from a R modifier, not from a brown(bb) on the B locus?

How would one distinguish a brown based chinchilla then, or rather is there such a thing? Would it be from the color of the basehairs?

For example, this buck:


His guard hairs and ears appear to carry brown, but his overall appearance(phenotype) is similar in shading to my dark chinchilla buck just with brown tips not black on his guard hairs.

Here is his parted coat photo, which appears to show a clear brown layer, then white, then a brown tip. I need a better fur pluck photo, but he's not as personable as my other rabbits yet.

 

[judymac]

How would one distinguish a brown based chinchilla then, or rather is there such a thing? Would it be from the color of the basehairs?

Chinchilla is just the regular agouti colors (black, blue, chocolate & lilac) with the yellowish bands removed. So the black-based chestnut/castor becomes a chinchilla (black chin), blue agouti (opal) becomes blue chin (squirrel), chocolate agouti becomes chocolate chin, and lilac agouti (lynx) becomes lilac chin. On the left is a young black chinchilla, the right a young chocolate chinchilla English Angora:

When they are young, they look just like normal chestnut and chocolate agouti rabbits:

When the kits' banding grows out, you can see that the middle agouti band is pearly white instead of yellowish.

 

[reh]

The yellow of rusty back is in the pheomelanin band, which is normally white in chin.

 

[reh]

There are rabbits withoutMC1R receptors, looking pale yellow:

 

[judymac]

There are rabbits withoutMC1R receptors, looking pale yellow:

Fascinating. Would these be like the Lutino rabbits, with pink eyes?

 

[judymac]

There are rabbits withoutMC1R receptors, looking pale yellow:

@reh , In reading the link to the research, I noticed something that seems to be cropping up fairly often--that the black rabbits are E(D) instead of just E. Is this because the Chinese black and checkered rabbits they are using just happen to be E(D), or is E(D) a whole lot more common than originally postulated? How would we know if our black rabbits were E(D) instead of E, other than agouti kits cropping up out of black-self looking parents?

 

[judymac]

Therefore the Japanese factor is actually recessive towards the nonextension gene in the light areas, whilst it is dominant towards the normal extension in the dark areas.

Is this why rabbits with only one copy of e(j) are still harlequinized? Because the e(j) black fills in the agouti areas just like E(D) would?

 

[reh]

Is this why rabbits with only one copy of e(j) are still harlequinized? Because the e(j) black fills in the agouti areas just like E(D) would?

Yes, but it behaves more like ES, so EEJ look like a mosaik of agouti and steel.
And thats also, why agouti doesnt matter in eJeJ ones - there are no receptors in light parts.

is E(D) a whole lot more common than originally postulated? How would we know if our black rabbits were E(D) instead of E, other than agouti kits cropping up out of black-self looking parents?

yes, f.e. in californians, checkered giants and NZW. And i think there is an american breed coming in blue/white/red only which would be explainable by this (if the reds are diluted and all are AA)
Unfortunately as far as i know nobody sequenced the complete MC1R of an steel looking rabbit (all ED ones are self looking or REW), so we do not know if there is ED and ES or only one of them (as some scientists suppose).
I know from one steel which had the same mutation as ED, but only 1/3 of the MC1R DNS was sequenced, so no evidence there is not another additional mutation like in chinchilla, which is an additional mutation of himalaya. I think, also regarding there history (ED occured much earlier), there is a different allele for ES.