Disease relevance of Ldhc

• Several cDNA clones for the mouse lactate dehydrogenase-X (LDH-X), a sperm-specific glycolytic enzyme, were isolated from mouse testicular cDNA libraries constructed in the bacteriophage vectors, lambda gt11 and gt10 [1].
• Its ultrastructural characteristics and the expression of genes that are transcribed in vivo in male germ cells (c-kit, LDH-X, and Hox a-4) suggest the progression of an initial, apparently pure Sertoli cell tumor into a mixed proliferation [2].
• Testicular lactic dehydrogenase isoenzyme activity (LDH-X), a pachytene spermatocyte marker of testicular toxicity, was significantly decreased to 71.8% and 68.6% of the control value after daily p.o. administration of ER (21 days) in doses of 68 and 136 mg kg-1 respectively [3].

High impact information on Ldhc

• A rabbit antiserum specific for LDH-X, the spermatozoal form of mouse lactate dehydrogenase, was prepared [4].
• A combination of sucrose gradient centrifugation and oligo(dT)-cellulose chromatography resulted in a 23-fold purification of LDH-X mRNA over total cytoplasmic testis RNA [5].
• Measurement of LDH-X mRNA levels in separated testis cell populations prepared by centrifugal elutriation demonstrated that LDH-X mRNA represents 0.17-0.18% of the total functional mRNA activity in fractions enriched in pachytene spermatocytes and round spermatids, but only 0.09-0.10% of the translation products of elongated spermatids [5].
• Total mouse testis RNA directs the synthesis of the sperm-specific C subunit of lactate dehydrogenase-X (LDH-X) when translated in a cell-free system derived from rabbit reticulocytes [5].
• ldhc expression in non-germ cell nuclei is repressed by NF-I binding [6].

Biological context of Ldhc

• A clone containing the 5' flanking region of the testis-specific murine lactate dehydrogenase C (Ldhc) gene was isolated from a mouse genomic library [7].
• The ldhc gene is active only in the germinal epithelium during spermatogenesis [8].
• We conclude that transcription of the transgene and possibly of the endogenous ldhc gene is restricted to leptotene/pachytene primary spermatocytes [8].
• The nucleotide and amino acid sequences of the mouse LDH-C cDNA show 73% and 72% homologies, respectively, with those of the mouse LDH-A [9].
• Molecular cloning and nucleotide sequence of the cDNA for sperm-specific lactate dehydrogenase-C from mouse [9].

Anatomical context of Ldhc

• The Northern blot analysis of poly(A)-containing RNAs from mouse testes and liver indicates that the LDH-C gene is expressed in testes but not in liver, and that its mRNA is approx. 1400 nucleotides in length [9].
• To determine whether the primate Ldhc mRNA is posttranscriptionally regulated, comparison of baboon and mouse Ldhc mRNA stability was made in a cell-free system [10].
• The binding of antibodies against LDH-X by preimplantation mouse embryos was studied to detect LDH-X from spermatozoa in embryos after fertilization [11].
• When the distribution of the LDH-X mRNA was examined across polysome gradients, both mRNAs were partially associated with polysomes [12].
• Silver grains accumulated in cells inside the second layer from the periphery of the seminiferous tubule, confirming previous findings that LDH-X mRNA first appears in the spermatocyte and continues to accumulate until the late spermatid stage [12].

Associations of Ldhc with chemical compounds

• Transgenic mice demonstrate a testis-specific promoter for lactate dehydrogenase, LDHC [8].
• Methylation of CpG dinucleotides alters binding and silences testis-specific transcription directed by the mouse lactate dehydrogenase C promoter [13].
• (1980) using antibodies to detect mutations in lactate dehydrogenase-C (LDH-C, previously called LDH-X) directly in sperm of mice exposed to the mutagen procarbazine [14].
• RNase H digestion of oligo (dT)-hybridized RNA and poly(U)-Sepharose column chromatography with differential elution by formamide revealed that the difference in size of the two classes of mRNAs was due to the poly(A) tail length of the LDH-X mRNA [12].
• After subcutaneous (s.c.) administration of cadmium (Cd), activity of lactate dehydrogenase isozyme-X (LDH-X) appeared in the serum of treated mice within 24 h [15].

Other interactions of Ldhc

• The 2 genes were found to be oriented in head-to-tail fashion with about a 6-kilobase (kb) distance between the 3' end of ldha and the 5' end of ldhc [16].

Analytical, diagnostic and therapeutic context of Ldhc

• The Southern blot analysis of genomic DNAs from mouse liver and human placenta indicates the presence of multiple LDH-C gene-related sequences [9].
• We demonstrate that polymerase chain reaction amplifies cytoplasmic DNAs with the expected intronless-structure of endogenous reverse transcriptase copies of the processed lactate dehydrogenase C mRNA encoding the testis-specific isoform of lactate dehydrogenase [17].
• LDH-X levels in the testis were analyzed by western immunoblot and ELISA [18].
• There was, however, a moderate inhibitory effect on fertilization in vitro, which may be attributable to a direct action of antiserum to LDH-X on sperm [4].
• Thus, in the fluorescent antibody technique, mouse sperm carrying normal LDH-X do not stain but the sperm containing mutated enzyme do stain [19].

References