Disease relevance of Lcn8

• After cryptorchidism or busulfan treatment, mEP17 levels were either greatly diminished or not detected [1].
• Introduction of specific mutations in the EP17 region that abolish induction by hypoxia, also eliminated the binding of one or both of these factors [2].

High impact information on Lcn8

• Here, we reported that the 1.8-kb Lcn5 promoter confers epididymis region-specific gene expression in transgenic mice [3].
• Murine epididymal retinoic acid-binding protein [or lipocalin 5 (Lcn5)] is synthesized and secreted by the principal cells of the mouse middle/distal caput epididymidis [3].
• The sequence -61 to -45 (EP17) relative to the transcription start of the murine epo gene imparted an approximately 4-fold induction of reporter gene expression due to hypoxia [2].
• The EP17 sequence is required for the 3' enhancer element of the epo gene to be maximally functional [2].
• We have previously reported that two lipocalin genes, mERABP (mouse epididymal retinoic acid binding protein), and mEP17 (mouse epididymal protein of 17 kDa), derived from an ancestral gene, are specifically expressed in the epididymis [1].

Biological context of Lcn8

• Significant caput epididymidis-specific CAT activity was detected in transgenic mouse lines; and CAT gene expression is restricted to the initial segment, as is the expression of the endogenous mEP17 gene [4].
• Altogether, our data demonstrate that mEP17 spatial expression, regulation, and fate are different from that of the highly related mouse epididymal retinoic acid binding protein [1].
• To identify cis-DNA regulatory element(s) involved in the tissue- and region-specific expression of the mEP17 gene in transgenic mice, we have studied the expression of a transgene containing 5.3 kb of the 5'-flanking region of the mEP17 gene (5.3mEP17) linked to chloramphenicol acetyltransferase (CAT) reporter gene [4].
• Lipocalin 5 [Lcn5 or epididymal retinoic acid-binding protein (E-RABP)] is a member of this epididymis-specific lipocalin gene cluster, which binds hydrophobic molecules such as retinoic acid [5].

Anatomical context of Lcn8

• Identification, immunolocalization, regulation, and postnatal development of the lipocalin EP17 (epididymal protein of 17 kilodaltons) in the mouse and rat epididymis [1].
• This suggests that mEP17 is dependent on testicular factor(s) that may have a germ cell origin [1].
• These cells express the androgen receptor as well as markers of the murine epididymal epithelium, PEB-like protein (ie, phosphatidye ethanolamine binding protein), E-RABP (ie, epididymal retinoic acid-binding protein), and EP17 (ie, epididymal protein of 17 kd) [6].

Associations of Lcn8 with chemical compounds

• After bilateral orchiectomy, mEP17 disappeared 2 d after surgery and was not restored after testosterone replacement [1].
• We have previously shown that the 5kb promoter fragment of the Lcn5 gene confers both androgen-dependent regulation and epididymis-specific gene expression in transgenic mice whereas 0.6kb promoter fragment does not [5].

Analytical, diagnostic and therapeutic context of Lcn8

• After unilateral orchiectomy, mEP17 levels decreased only in the orchiectomized side [1].

References