Disease relevance of Pax1

• In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing [1].
• Using the human PDGFRalpha promoter linked to a luciferase reporter, we show in the present paper that Pax1 acts as a transcriptional activator of the PDGFRalpha gene in differentiated Tera-2 human embryonal carcinoma cells [2].
• Surprisingly, Pax1 mutant proteins appear to have opposing transcriptional activities in undifferentiated Tera-2 cells as well as in the U-2 OS osteosarcoma cell line [2].
• Pax1/E2a double-mutant mice develop non-lethal neural tube defects that resemble human malformations [3].
• The scoliosis (sco) mouse: a new allele of Pax1 [4].

High impact information on Pax1

• The tendon progenitors are induced at the sclerotome's edge, at the expense of skeletogenic Pax1 positive cells and in response to FGF signaling in the adjacent myotome [5].
• Interaction between undulated and Patch leads to an extreme form of spina bifida in double-mutant mice [6].
• The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column [7].
• In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present [7].
• We localized the Pax 1 gene on chromosome 2 between beta 2-microglobulin and the agouti locus to an area where un maps [8].

Chemical compound and disease context of Pax1

• Early loss of estrogen in the null mutants leads to obesity and skeletal abnormalities that intensify with age producing (kyphosis), a hunchback appearance [9].

Biological context of Pax1

• However, mutation of the Pax1 gene is responsible for the un phenotype, but the Pax1 gene in the kkt mice is not rearranged or deleted [10].
• The transgene is integrated at the distal end of chromosome 2 close to the Pax1 gene, as revealed by FISH analysis [10].
• Some skeletal malformations encountered in Hoxa5 mutants are shared by the undulated (un) mice, which bear a point mutation in the Pax1 gene [11].
• Our genetic studies show that Hoxa5 and Pax1 cooperate in the vertebral patterning of the cervicothoracic transition region and in acromion morphogenesis [11].
• Parathyroids were also reduced in Pax1(-/-) mutants, revealing a new function for Pax1 in parathyroid organogenesis [12].

Anatomical context of Pax1

• Pax1 is expressed normally in kkt embryos and in the thymus of mature animals, and there is no mutation in its coding sequence [10].
• Remarkably, Nkx2-2 is ectopically activated in the sclerotome and limb buds of Pax1(Un-s) embryos, both of which normally express Pax1 [13].
• The paraxial mesoderm shows evidence of ventralisation, with increased expression of the sclerotomal marker Pax1, and diminished expression of the dermomyotomal marker Pax3 [14].
• We have previously shown that the paired-box transcription factors Pax1 and Pax9 synergistically act in the proper formation of the vertebral column [15].
• In contrast, notochord is required to induce Pax1 in competent sclerotomes [16].

Associations of Pax1 with chemical compounds

• In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides [17].
• Inhibition curves parallel with the standard were, however, obtained on dissociation of the high mol. wt. protein complex with sodium dodecyl sulfate [18].
• The 116,000-mol wt protein was detected as a triplet on protein blots until 13 days after estrogen withdrawal, when diminution in the intensity of the highest mol wt triplet protein was noted [19].
• Furthermore, ASSAM immunoreactivity appeared in the low mol wt proteins (below 10,000 daltons) of apo HDL separated in the buffer containing 8 M urea through Sephadex G-200 [20].
• Treatment of Ss with C1 cleaves a 7,000-8,000-mol wt fragment from the alpha-chain [21].

Physical interactions of Pax1

• The Sd gene is known to interact with undulated (un), a sclerotome mutant [22].

Regulatory relationships of Pax1

• Noggin and Shh induce Pax-1 synergistically [23].

Other interactions of Pax1

• In contrast, the medial sclerotomal marker Pax1 is expressed normally in mutant embryos, arguing that Pax3 is not required for development of the medial sclerotome [24].
• In contrast, Pax1 expression in all pharyngeal pouches requires both Eya1 and Six1 function [25].
• Taken together, we propose that a combination of a loss-of-function mutation of Pax1 and a gain-of-function mutation of Nkx2-2 is the molecular basis of the Pax1(Un-s) mutation [13].
• It is therefore apparent that these two mutations do not fully complement each other, and we propose that a gene in the kkt locus possesses a unique role that functions in concert with Pax1 during skeletal development [10].
• Nevertheless, downstream events of the Pax1/Pax9 action and their target genes remain to be elucidated [15].

Analytical, diagnostic and therapeutic context of Pax1

• RNA in situ hybridization for the transcription factors Hoxa3 and Pax1 was used to investigate the basis of this defect [26].
• Using Sephadex G-200 gel chromatography, SASSAM was eluted as a high mol wt form of approximately 200,000 daltons [20].
• The active factor(s) sedimented at approximately 7S on sucrose gradient centrifugation and eluted from 4B Sepharose in the region of 170,000 mol wt proteins [27].
• Both sets of antibodies labeled a 71,000 mol. wt protein in Western blots of synaptic membranes obtained from either rat or bovine brain, an indication of homology between these proteins [28].
• Peptide mapping of individual pituitary proteins within the gel after separation by electrophoresis in NaDodSO4-polyacrylamide gels has revealed a high-molecular-weight (mol wt) protein whose fingerprint is similar to that of prolactin (PRL) [29].

References