Psoriasis

Causes

This disease is associated with:

·         Presence of nucleated cells in corneum.

·         Removal of nuclear material from keratinocytes and just keratin is filled in it.

·         Because of this removal of nuclear material keratinocytes don not degrade their nuclear material and DNA enters into corneum.

This condition is because of the deficiency of DNAse2.

Explanation:

When we talk about mice the deficiency of DNAse2 causes the mice:

·         Not to degrade its nuclear material.

·         Fragile hairs.

·         Maturation defects of hair.

This shows that presence of DNAse2 is necessary for the degradation of nuclear material. As DNAse2 is present in hair and skin. So, in order to remove or degrade nuclear material DNAse2 is necessary otherwise DNA will be still present in skin and hair. SNPs are responsible for the degradation of DNAse2.These SNPs are responsible for psioriasis.In autoimmunity of skin DNAse2 is also responsible. Due to autoimmunity of skin inflammation is caused on skin.DNAse2 prevents from this inflammation because it removes nuclear material from skin.DNAse2 works best at Ph below 7.Due to aciditification of cytosol.It DNAse2 becomes activated. Overall, major role of DNAse2 is in degradation of nuclear material.

Inflammatory anemia:

Causes:

In mice the DNAse2a which is present is involved in many diseases that are linked with autoimmunity. This DNAse2a is responsible for embryonic lethality. Main reason of this embryonic lethality is inflammatory anemia.DNAse2a degrades red blood cells. When red blood cells are developed in mouse and human their nuclei is removed and this nuclei is used by macrophages. The DNA that is present in RBCs is used by DNAse2a and macrophages. When DNAse2a and macrophages can not degrade DNA than activation of STING occurs which causes production of interferon type1.

Although DNAse2a is necessary for the development of mice to its adulthood but it can also cause disease like mice can develop rheuminated arthritis.

Experiment:

An experiment was performed with mice. In this experiment bone marrow that was deficient of DNAse2a was implanted in mice. This experiment was performed to observe deficiency associated with removal of DNAse2a.

Results:

·         Mice developed arthritis because of activation of STING.

·         Inflammatory phenotypes can be reversed by STING.

·         STING also promotes survival.

·         Dan sensors also cause arthritis.

Deficiency of DNAse2a:

Its deficiency severely affects life of organism. Its deficiency causes:

·         Degradation of nuclear material is affected.

·         Thymus and kidney are greatly affected its removal.

·         Production of sebum is affected.

·         Programmed cell death is affected.

On the whole presence of DNAse2a is necessary for the survival of organisms.

Cataracts:

Causes:

This disease is associated with DNAse2b.This DNAse2b is responsible during lens development. DNA must be removed during lens development because it is required for the clarity of lens. DNase is very necessary for this clarity of lens because as it is involved in the removal of DNA so, if DNA is not removed than lens vision would be blurr.This condition develops cataracts.HSF4 is responsible for the regulation of DNAse2a.When deficiency occurs in HSF4 than cataracts are developed because deficiency in DNAse2b has occurred.DNAse2b removes DNA from fiber cells. When organs are subjected to breakdown than DNAse2b leaves the secretary system and than it enters lens cells and gains access to nuclei.

Different types of organisms uses different types of DNases for the clearance of lens. In case of zebra fish DNAse1 is required for the clearance of lens instead of using DNAse2b.This is because DNAse2b works best at Ph below 7.DNAse2b also has greater role in lungs and salivary glands.

Pseudomonas sensitivity:

This disease is caused because of L-DNAse2 and SerpinB1.Both of these also cause infection of lungs. When experiments were performed with mice differences were not clear. One mice was given L-DNAse2 and SerpinB1 and other was not given. When both of these mice were observed there were no clear differences between both of these mice until the mice that was given these DNases developed infection. In the infected mice there was neutrophil death. The reason for this neutrophil death is NET production was inhibited by SerpinB1.

In condensation of chromatin SerpinB1 is involved.LDNAse2 releases NLS. It is also possible that pseudomonas sensitivity may be because of LDNAse2 instead of SerpinB1.The activity of DNase 2 and 1 cant be compared with LDNAse2.This information is important. This was all about the significance of DNases in clinical point of view.