Targeted inactivation of Hoxb8 affects survival of a spinal ganglion and causes aberrant limb reflexes

Abstract

Hoxb8 mutant mice were generated by inserting the lacZ coding sequence in frame with the first exon of Hoxb8. These mice express a fusion protein with a functional beta-galactosidase activity instead of Hoxb8. Mutant embryos were analyzed for anatomical changes. The results indicate that Hoxb8 is not an indispensable regulator of A-P patterning in the forelimb, unlike suggested by our Hoxb8 gain of function experiments (Charité J, DeGraaff W, Shen S, Deschamps J. Cell 1994;78:589-601). The null mutant phenotypic traits include degeneration of the second spinal ganglion (C2), an abnormality opposite to the alteration in the gain of function transgenic mice. Subtle changes in the thoracic part of the vertebral column were observed as well. Adult homozygous mutants exhibit an abnormal clasping reflex of the limbs.

Brain-Derived Neurotrophic Factor Is Required for the Establishment of the Proper Number of Dopaminergic Neurons in the Substantia Nigra Pars Compacta

“…At early ages, Wnt-BDNF KO mice display a clutching phenotype similar to that seen in other mouse models of neurodegeneration (Lalonde, 1987a;Hamilton et al, 1996;van den Akker et al, 1999;Auerbach et al, 2001;Guidetti et al, 2001). Wnt-BDNF KO mice also display significant deficits in motor ability as assayed by rotarod, yet their improvement in successive trials demonstrates that they are capable of motor learning.…”

Randomly inserted and targeted Hox/ reporter fusions transcriptionally silenced in Polycomb mutants

“…The Hoxb8lacZ (15) and Hoxc8lacZ (16) knock-in mouse lines were described earlier, as were transgenic Hoxb8lacZ (17), Hoxb7lacZ (18), and Hoxb1lacZ (19). The Hoxb9AlkPhos͞Hoxb8lacZ transgene was generated by recombining a Hoxb9AlkPhos construct made by J. Sharpe (National Institute for Medical Research, London) and R. Krumlauf (The Stowers Institute for Medical Research, Kansas City, MO) (see ref.…”

Early Striatal Dendrite Deficits followed by Neuron Loss with Advanced Age in the Absence of Anterograde Cortical Brain-Derived Neurotrophic Factor

“…KO mice display phenotypic behavior indicative of motor dysfunction Hindlimb and forelimb clasping have been observed in transgenic lines in which there is motor dysfunction or degeneration, including HD mouse models expressing mutant huntingtin, Hoxb8 knock-outs, and staggerer mutants in the RORalpha gene (Lalonde, 1987;Hamilton et al, 1996;van den Akker et al, 1999;Auerbach et al, 2001;Guidetti et al, 2001;van Dellen et al, 2001). Given the proposed role of Htt as an activator of cortical BDNF transcription , we tested the response of Emx-BDNF KO mice to tail suspension at varying ages (1-12 months).…”