Posted 11 October 2010

General Information

The Tardbp gene, was isolated from a C57BL/6 genomic BAC clone (RP23-331p21; BACPAC). Conditional Tardbp-KO mouse line generated by engineering a targeting vector in which the 3rd exon of Tardbp was flanked by loxp together with a neomycin resistance gene inserted in the 2nd intron; The neomycin cassette was subsequently deleted through a crossbreeding strategy with hACTB-flp transgenic mice. The floxed Tardbp mice were crossbred with a CAG-Cre transgenic mouse line that express the Cre recombinase ubiquitously to generate the heterozygous Tardbp-KO (Tardbp+/-) mice.

Mutation: Conditional deletion of exon 3 of Tardbp.

Promoter: N/A

Mouse strain: V26.2 C57BL/6j ES cells; injected into albino C57BL/6J; Background: C57BL/6; Generation: F3, N3.

Phenotype

Neuropathological analysis:

Behavioral Phenotype:

Tardbp+/- mice were fertile and expressed similar level of TDP-43 in a variety of tissues compared with those of Tardbp+/+ mice. Postnatal deletion of Tardbp in mice caused dramatic loss of body fat followed by rapid death. Moreover, conditional Tardbp-Ko ES cells failed to proliferate.

Availability

Contact: Philip C. Wong
Department of Pathology, Division of Neuropathology
The Johns Hopkins University School of Medicine
558 Ross Research Building
720 Rutland Avenue
Baltimore, Maryland 21205-2196
Phone: 410-502-5168
Fax: 410-955-9777
E-mail: Philip C. Wong

References

Primary:

Chiang P-M, Ling J, Jeong H-Y, Price DL, Aja SM, Wong PC. Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. PNAS 107:16320, 2010. Abstract

Associated:

Shan, X, Chiang P-M, Price DL and Wong, PC. Altered distribution of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. PNAS 107:16325, 2010. Abstract