Comparative Analysis of the Expression Profile of Wnk1 and Wnk1/Hsn2 Splice Variants in Developing and Adult Mouse Tissues
نویسندگان
چکیده
The With No lysine (K) family of serine/threonine kinase (WNK) defines a small family of kinases with significant roles in ion homeostasis. WNK1 has been shown to have different isoforms due to what seems to be largely tissue specific splicing. Here, we used two distinct in situ hybridization riboprobes on developing and adult mouse tissues to make a comparative analysis of Wnk1 and its sensory associated splice isoform, Wnk1/Hsn2. The hybridization signals in developing mouse tissues, which were prepared at embryonic day e10.5 and e12.5, revealed a homogenous expression profile with both probes. At e15.5 and in the newborn mouse, the two probes revealed different expression profiles with prominent signals in nervous system tissues and also other tissues such as kidney, thymus and testis. In adult mouse tissues, the two expression profiles appeared even more restricted to the nervous tissues, kidney, thymus and testis, with no detectable signal in the other tissues. Throughout the nervous system, sensory tissues, as well as in Cornu Ammonis 1 (CA1), CA2 and CA3 areas of the hippocampus, were strongly labeled with both probes. Hybridization signals were also strongly detected in Schwann and supporting satellite cells. Our results show that the expression profiles of Wnk1 isoforms change during the development, and that the expression of the Wnk1 splice variant containing the Hsn2 exon is prominent during developing and in adult mouse tissues, suggesting its important role in the development and maintenance of the nervous system.
منابع مشابه
WNK1/HSN2 Mutation in Human Peripheral Neuropathy Deregulates KCC2 Expression and Posterior Lateral Line Development in Zebrafish (Danio rerio)
Hereditary sensory and autonomic neuropathy type 2 (HSNAII) is a rare pathology characterized by an early onset of severe sensory loss (all modalities) in the distal limbs. It is due to autosomal recessive mutations confined to exon "HSN2" of the WNK1 (with-no-lysine protein kinase 1) serine-threonine kinase. While this kinase is well studied in the kidneys, little is known about its role in th...
متن کاملWNK1/HSN2 isoform and the regulation of KCC2 activity
Hereditary sensory and autonomic neuropathy type 2 is a rare autosomal recessive pathology presenting with early onset peripheral sensory defects. It arises from mutations affecting a specific isoform of the WNK1 kinase (with-no-lysine protein kinase 1) termed WNK1/HSN2. The role of WNK1 in the nervous system is not well understood. In our recent paper, we examined the effect of a pathological ...
متن کاملA New Methodology for Quantification of Alternatively Spliced Exons Reveals a Highly Tissue-Specific Expression Pattern of WNK1 Isoforms
Mutations in the WNK1 gene, encoding a serine-threonine kinase of the WNK (With No lysine (K)) family, have been implicated in two rare human diseases, Familial Hyperkalemic Hypertension (FHHt) and Hereditary Sensory and Autonomic Neuropathy type 2 (HSAN2). Alternative promoters give rise to a ubiquitous isoform, L-WNK1, and a kidney-specific isoform, KS-WNK1. Several other isoforms are generat...
متن کاملMutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.
Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. ...
متن کاملPathogenesis of spinal cord injury induced edema and neuropathic pain: expression of multiple isoforms of wnk1
BACKGROUND Neuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na(+)-K(+)-Cl(-) 1 (NKCC1), phosphorylation profile of NKCC1 and its speci...
متن کامل