Posted 11 October 2010

General Information

Human TDP-43 cDNA was subcloned into a mouse Thy1.2 expression cassette and subsequently injected into C57BL/6;SJL hybrid mouse embryos.

Mutation: Human TDP-43.

Promoter: Thy 1.2.

Mouse strain: C57Bl6/J. Background strain: C57BL/6; SJL; Background: C57BL/6; Generation: F3N2.

Phenotype

Neuropathological analysis:

Male mice from groups W2 and W3 abruptly develop severe tremor, abnormal reflex of hindlimbs and gait abnormalities within a short time window, postnatal day 14 to dsy 18. Females develop fine tremor only after three months of age.

Behavioral Phenotype:

TDP-43 mice exhibited retardation of development when compared with non-transgenic littermates. Severities of this phenotype correlated with the copy number of the transgene. W1 with the highest transgene copy were smaller than non-tg and die within 3wks of age. W2 and W3 with lower number of transgene exhibit less growth retardation and grow to adulthood. Male mice show 20% growth reduction compared to female mice.

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:

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. Abstract

Associated:

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