Disease relevance of Kap

• Kap expression is under multihormonal control, and hormonal changes in DHA-induced nephrolithiasis may account for the decreased Kap expression in APRT-deficient mice [1].

High impact information on Kap

• The administration of testosterone to females or castrated males results in the induction of KAP mRNA to normal male levels [2].
• KAP mRNA is not found in significant amounts in tissues other than the kidney, and the KAP gene renatures with kinetics similar to single-copy DNA [2].
• A KAP cDNA fragment was purified and used for nucleic acid hybridization studies [2].
• With the rapidly expanding knowledge of mouse genetics, KAP should prove useful in determining genetic factors which regulate the inducibility and tissue specificity of a hormonally regulated gene [2].
• The gene for kidney androgen-regulated protein (KAP) is the most abundant and specific gene expressed in mouse kidney proximal tubule cells, where it is tightly regulated by steroid and thyroid hormones in different tubule segments [3].

Chemical compound and disease context of Kap

• We previously observed a significant decrease in Kap mRNA expression in whole kidney tissue from male mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis [1].

Biological context of Kap

• These results indicate that KAP gene expression is subject to cell-specific regulation in different segments of the proximal tubule and that this regulation is mediated by hormones of both gonadal and pituitary origin [4].
• Nucleotide sequence of kidney androgen-regulated protein mRNA and its cell-specific expression in Tfm/Y mice [5].
• Dihydrotestosterone (DHT) stimulated in an androgen-dependent manner the transactivation of KAP in PCT and PR cells, while mutation of a putative androgen-response element (ARE) sequence located at -39 bp from the transcription initiation site abolished the transactivation induced by DHT [6].
• Transient transfection studies with different KAP promoter constructs indicated that a 224 bp-truncated fragment was sufficient to mediate cell-specific expression of the KAP promoter [6].
• After conducting a differential screen of a mouse uterus cDNA library, a clone was identified that is identical to KAP [7].

Anatomical context of Kap

• Kidney androgen-regulated protein (KAP) gene expression is under androgenic control in the epithelial cells of the proximal convoluted tubule in the mouse kidney [4].
• Kidney androgen-regulated protein gene is expressed in the uterus during late pregnancy [7].
• As determined by in situ hybridization analysis, epithelial cells of proximal convoluted tubules of cortical nephrons express KAP mRNA in response to androgenic stimulation while similar cells in the juxtamedullary S3 segment of the tubules express KAP mRNA under estrogenic and pituitary hormonal control [8].
• The addition of 30 nM DHT to the steroid-free medium resulted in a slight increase in Gus and in a more marked increase in KAP transcripts in both cell lines [9].
• Furthermore, using an anti-ARP antibody that recognizes both ARP1 and EAR3 we show that these ARP subfamily member(s) present in keratinocytes bind to both RAREs [10].

Associations of Kap with chemical compounds

• Treatment of Tfm/Y animals with testosterone caused a partial induction of KAP mRNA levels, while dihydrotestosterone had no effect [4].
• Kidney androgen-regulated protein (KAP) mRNA is an abundant renal mRNA that was originally identified by comparisons of the products of in vitro translation of poly(A) RNA from animals before and after androgen stimulation [5].
• Estrogen treatment of Tfm/Y mice caused an increase in KAP gene expression similar to that observed with testosterone [4].
• Effects of thyroid hormone on the androgenic expression of KAP gene in mouse kidney [11].
• Results in hyt/hyt mice after treatment with retinoic acid, alone or in combination with TH, demonstrated that this regulator does not have any effect on the regulation of the KAP gene in mouse kidney and that induction of the gene by T3 does not require heterodimerization of TR with retinoic acid-related receptors [12].

Regulatory relationships of Kap

• Examination of sections of kidneys from Tfm/Y mice before and after testosterone (T) treatment revealed that only the juxtamedullary tubules expressed KAP mRNA and that T increased the level of KAP mRNA in these cells [13].

Other interactions of Kap

• These data suggested that the androgen receptor-independent induction of KAP gene expression in these animals was mediated by an estrogenic metabolite of testosterone, since dihydrotestosterone cannot be aromatized to an estrogenic form [4].
• Mice treated with thyrotropin (TSH), follitropin (FSH), and lutropin (LH) exhibited high levels of KAP mRNA in S3 cells of females as well as in the renal cortex of male animals [8].
• Furthermore, insulin-like growth factor 1 (IGF-1), but not T(3), enhanced the androgen-dependent transactivation of KAP in cultured PCT cells [6].
• In 1-month-old APRT-deficient male mice, Kap expression was decreased significantly and was undetectable in female mice [1].
• Reporter gene expression directed by a 1542-base pair (bp) fragment of the Kap promoter is specific to the proximal tubules of the kidney and androgen-regulated [14].

Analytical, diagnostic and therapeutic context of Kap

• In Tfm/Y androgen receptor-deficient mice, KAP mRNA was detected by in situ hybridization in a subpopulation of these cells only in the S3 segment of the proximal tubules in the outer medulla [4].
• After castration, only tubules in the outer stripe of the medulla express KAP mRNA [5].
• However, ovariectomy of normal female mice did not eliminate KAP gene expression in the S3 cells and, in fact, resulted in a slight increase [4].
• However, hypophysectomy alone completely eliminated this cell-specific component of KAP gene expression [4].
• Kap mRNA was not detected in 3- or 6-month-old mice using our standard ISH protocol, but we observed intense cytoplasmic staining in S3 proximal tubules in wild-type male mice of these age groups using an improved RT-PCR ISH procedure [1].

References