Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

Abstract

Jimpy (Plp jp ) is an X-linked recessive mutation in mice that causes CNS dysmyelination and early death in affected males. It results from a point mutation in the acceptor splice site of myelin proteolipid protein (Plp) exon 5, producing transcripts that are missing exon 5, with a concomitant shift in the downstream reading frame. Expression of the mutant PLP product in Plp jp males leads to hypomyelination and oligodendrocyte death. Expression of our Plp-lacZ fusion gene, PLP(+)Z, in transgenic mice is an excellent readout for endogenous Plp transcriptional activity. The current studies assess expression of the PLP(+)Z transgene in the Plp jp background. These studies demonstrate that expression of the transgene is decreased in both the central and peripheral nervous systems of affected Plp jp males. Thus, expression of mutated PLP protein downregulates Plp gene activity both in oligodendrocytes, which eventually die, and in Schwann cells, which are apparently unaffected in Plp jp mice.

The Expression of TAG-1 in Glial Cells Is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS

“…The PLP protein is predominantly expressed in oligodendrocytes but plp gene products have also been detected in Schwann cells Wight et al, 1993Wight et al, , 2007Griffiths et al, 1995;Garbern et al, 1997). Immunostaining in live, P4, cultured Schwann cells from Tag-1 Ϫ/Ϫ ;plp Tg (rTag-1 ) mice after 4 DIV showed that rTAG-1 is expressed on the cell surface of Schwann cells in a similar pattern as was previously reported for normal rats (data not shown) (Traka et al, 2002).…”

Constitutively Active Akt Induces Enhanced Myelination in the CNS

“…The Plp gene is expressed in Schwann cells (Puckett et al 1987), and our transgene promoter is expressed in both myelinating and nonmyelinating Schwann cells (Jiang et al 2000; Wight et al 2007). Expression of Akt in sciatic nerve was elevated in Plp -Akt DD mice at 3 months (Fig.…”

Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis

“…Six-to eight-week female C57BL/6 or SJL mice were used in all experiments. In some studies to facilitate detection of oligodendrocyte lineage cells, female mice from the enhanced green fluorescent protein (EGFP) transgenic strain on a C57BL/6J background expressing EGFP driven by the promoter from the myelin proteolipid protein (plp) gene (Wight et al, 2007) were used. Standard C57BL/6 and SJL mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and chronic EAE was induced in the C57BL/6 animals by subcutaneous immunization with 200 lL of 200 lg MOG 35-55. Relapsing-remitting EAE was induced in SJL mice by subcutaneous immunization with 150 lg PLP 139-151 .…”