Human midsized neurofilament subunit induces motor neuron disease in transgenic mice.

Aberrant accumulation of neurofilaments is a feature of human motor neuron diseases. Experimentally motor neuron disease can be induced in transgenic mice by overexpressing the mouse neurofilament light subunit (NF-L), the human heavy subunit (NF-H), or mouse peripherin. Here we describe that mice harboring a bacterial artificial chromosome (BAC) transgene containing the human midsized neurofilament subunit (NF-M) gene develop a progressive hind limb paralysis associated with neurofilamentous accumulations in ventral horn motor neurons and axonal loss in ventral motor roots.

Ectopic expression of Gcm1 induces congenital spinal cord abnormalities.

Brief ectopic expression of Gcm1 in mouse embryonic tail bud profoundly affects the development of the nervous system. All mice from 5 independently derived transgenic lines exhibited either one or both of two types of congenital spinal cord pathologies: failure of the neural tube to close (spina bifida) and multiple neural tubes (diastematomyelia). Because the transgene is expressed only in a restricted caudal region and only for a brief interval (E8.

Neurofilament-M interacts with the D1 dopamine receptor to regulate cell surface expression and desensitization.

We used the yeast two-hybrid assay to identify novel proteins that interact with the D(1) dopamine receptor. The third cytoplasmic loop (residues 217-273) of the rat D(1) receptor was used as bait to identify clones encoding interacting proteins from a rat brain cDNA library. This identified two clones encoding the C terminus of rat neurofilament-M (NF-M) (residues 782-846).

Gcm1 expression defines three stages of chorio-allantoic interaction during placental development.

The formation of the labyrinth layer is a critical step of placental development. The transcription factor glial cells missing 1 (Gcm1) plays a pivotal role in labyrinth development, but the sequence of events controlling its expression has not been identified yet. Our studies presented herein show that Gcm1 expression occurs in three distinct phases during placental development, each specific to a particular stage of chorio-allantois interaction.

HUMAN MIDSIZED NEUROFILAMENT EXPRESSION IN TRANSGENIC MOUSE-DERIVED GRAFTS FACILITATES STUDY OF GRAFT-HOST INTERACTIONS IN HYPOGONADAL MICE.

Our previous studies established that targeted axonal outgrowth into the host median eminence (ME) from grafted gonadotropin-releasing hormone (GnRH) neurons is essential for stimulation of reproductive function in hypogonadal (HPG) mice homozygous for a deletion in the GnRH gene. In the current experiments transgenic mice expressing the human midsized neurofilament NF(M) were used as sources of grafts to clarify the extent of transplant-derived innervation of the host that accompanies this dramatic recovery process. Preoptic area (POA) tissue from 1- or 2-dayold transgenic pups was implanted in the third ventricle of adult male HPG mice.