Disease relevance of Crisp1

• We have now isolated and characterized overlapping phage clones covering the entire length of the CRISP-1 gene [1].
• Further studies will reveal to what extent the absence or the non-functionality of SCP1 contributes to male infertility [2].
• NW-BR-2 is identical to the CT antigen SCP-1, initially isolated by SEREX analysis of renal cancer [3].
• Identification of tumor-restricted antigens NY-BR-1, SCP-1, and a new cancer/testis-like antigen NW-BR-3 by serological screening of a testicular library with breast cancer serum [3].

High impact information on Crisp1

• The protein shares homology with the mammalian cysteine-rich secretory protein (CRISP) family that includes testes-specific spermatocyte protein 1, a cell adhesion protein which links spermatocytes to Seritoli cells, and acidic epididymal glycoproteins that bind to sperm and have been implicated in sperm-egg fusion [4].
• The cysteine-rich secretory protein domain of Tpx-1 is related to ion channel toxins and regulates ryanodine receptor Ca2+ signaling [5].
• The first member of the cysteine-rich secretory protein (CRISP) family was described by our laboratory in the rat epididymis, and it is known as DE or CRISP-1 [6].
• The interesting finding that the binding site of DE resides in an evolutionarily conserved region of the molecule provides novel information on the molecular mechanisms underlying CRISP-1 function in gamete fusion with important implications on the structure-function relationship of other members of the widely distributed CRISP family [6].
• To test this possibility we used the yeast two-hybrid system and found that the N-terminal end of the SCP1 protein indeed strongly interacted with itself, but not with other protein domains tested [7].

Biological context of Crisp1

• Acidic epididymal glycoprotein (AEG) is an androgen-regulated, epididymal secretory protein assumed to be involved in sperm maturation [8].
• AA1 also showed significant amino acid sequence homology with other cysteine-rich secretory proteins (CRISP's): rat and mouse acidic epididymal glycoproteins (AEG; also known as proteins D/E in rats) and helothermine, a toxin from the Mexican beaded lizard [9].
• A down-regulation of CRISP-1 expression was also observed in the epididymis [10].
• In the salivary gland, CRISP-1 and to a lesser extent CRISP-3 expression was markedly reduced, in spite of an up-regulation of androgen receptor transcript levels [10].
• The nucleotide sequence of Aeg-1 cDNA clones was identical to that of epididymis-expressed Aeg cDNA clones, indicating that Aeg-1 is expressed in both epididymides and SMGs [8].

Anatomical context of Crisp1

• In the present study, we show that the mouse submandibular gland (SMG) expresses two genes designated Aeg-1 and Aeg-2 [8].
• Autoantigen 1 of the guinea pig sperm acrosome is the homologue of mouse Tpx-1 and human TPX1 and is a member of the cysteine-rich secretory protein (CRISP) family [9].
• RT-PCR analysis of RNA isolated from acinar cells of lacrimal glands revealed that they expressed CRISP-1 and CRISP-2 [11].
• Cysteine-rich secretory proteins (CRISPs) represent a family of evolutionarily conserved proteins which may play a role in the innate immune system and are transcriptionally regulated by androgens in several tissues [11].
• CRISP2, originally known as Tpx-1, is a cysteine-rich secretory protein specifically expressed in male haploid germ cells [12].

Associations of Crisp1 with chemical compounds

• The androgen dependency of the genes coding for the cysteine-rich secretory proteins (CRISP) was analysed in their main sites of expression [10].
• CRISP-1 and CRISP-3 RNA levels were significantly increased, and these effects were prevented by a concomitant treatment with the antiandrogen flutamide [10].
• Testosterone treatment of C3H/HeJ female mice was followed by an upregulation of the steady-state CRISP-1 but not CRISP-2 transcript levels [11].
• SGP28, a novel matrix glycoprotein in specific granules of human neutrophils with similarity to a human testis-specific gene product and a rodent sperm-coating glycoprotein [13].
• For heterologous expression, the CRISP-1 coding sequence was introduced into the pMPSV/CMV vector before transfection of baby hamster kidney (BHK) cells and selection with puromycin and neomycin [14].

Regulatory relationships of Crisp1

• Epididymal cysteine-rich secretory protein 1 encoding gene is expressed in murine hair follicles and downregulated in mice overexpressing Hoxc13 [15].

Other interactions of Crisp1

• The second, more abundant transcript, Aeg-2, had a sequence similar to, but distinct from, that of Aeg-1, and was not detectable in the epididymis [8].
• Mouse submandibular glands express an androgen-regulated transcript encoding an acidic epididymal glycoprotein-like molecule [8].
• 8. High levels of CRISP-1 antigen were detected in the corpus and cauda of the epididymis, vas deferens, seminal vesicle, prostate, and in the salivary gland by immunohistochemistry [14].
• Evaluation of the 5'-flanking regions of murine glutathione peroxidase five and cysteine-rich secretory protein-1 genes for directing transgene expression in mouse epididymis [16].
• In contrast to CRISP-1, the 5.0-kb 5' region of the mouse GPX5 gene directed EGFP expression to the epididymis [16].

Analytical, diagnostic and therapeutic context of Crisp1

• In situ hybridization of SMG sections showed that Aeg-1 and Aeg-2 transcripts are produced by the cells of granular convoluted tubules [8].
• The intron length, as determined by PCR, varied between 1.05 and 4.0 kb so that the CRISP-1 gene spans over 20 kb of the mouse genome [1].
• Crisp-1 is a single-copy gene as shown by the presence of single bands by Southern blot analysis and PCR using rat genomic DNA as template [17].
• A quantitative analysis of the cauda epididymal fluid by sandwich ELISA revealed that CRISP-1 represented approximately 15% of the total protein [14].
• We have now developed a new sensitive procedure for immunoelectron microscopy of synaptonemal complex proteins and determined the exact localization of the two nonhelical ends of the SCP1 protein within the mouse synaptonemal complex [7].

References