alexa Genetic background and gender effects on gross phenotypes in congenic lines of ALS2 alsin-deficient mice.
Genetics

Genetics

Molecular Biology: Open Access

Author(s): Hadano S, Yoshii Y, Otomo A, Kunita R, SuzukiUtsunomiya K, , Hadano S, Yoshii Y, Otomo A, Kunita R, SuzukiUtsunomiya K,

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Abstract Loss-of-function mutations in human ALS2 account for several juvenile recessive motor neuron diseases (MNDs). To understand the molecular basis underlying motor dysfunction in ALS2-linked MNDs, several lines of Als2(-/-) mice with a mixed genetic background were thus far generated, and their phenotypes were thoroughly characterized. However, several phenotypic discrepancies among different Als2-deficient lines became evident. To investigate whether genetic backgrounds are associated with such discrepancies, we here generated congenic lines of Als2(-/-) mice on two different genetic backgrounds; C57BL/6 (B6) and FVB/N (FVB), and investigated their gross phenotypes. Both B6 and FVB congenic lines were viable and fertile with no evidences for obvious abnormalities. There were no differences in growth curves between wild-type and Als2(-/-) mice on each genetic background. Remarkably, Als2(-/-) mice on a FVB, but not a B6, background exhibited a shorter life span than wild-type litters. Further, B6 female, but not male, Als2(-/-) mice showed a significantly lower spontaneous rearing activity than wild-type litters. These genetic background- and/or gender-specific findings suggest the presence of modifiers for life span and motor activities in Als2(-/-) mice. These congenic mice should provide a useful means to understand the molecular and genetic basis for variable expression of pathological phenotypes in MNDs. 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved. This article was published in Neurosci Res and referenced in Molecular Biology: Open Access

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