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

• Published in: Neuroscience research 2010-10, Vol.68 (2), p.131-136
• Main Authors: Hadano, Shinji, Yoshii, Yasuhiro, Otomo, Asako, Kunita, Ryota, Suzuki-Utsunomiya, Kyoko, Pan, Lei, Kakuta, Shigeru, Iwasaki, Yasuo, Iwakura, Yoichiro, Ikeda, Joh-E
• Format: Article
• Language: English
• Subjects: Als2 knockout mouse; ALS2/alsin; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - mortality; Amyotrophic Lateral Sclerosis - physiopathology; Analysis of Variance; Animals; Body Weight - genetics; Disease Models, Animal; Female; Gender; Genetic background; Guanine Nucleotide Exchange Factors - deficiency; Longevity - genetics; Male; Mice; Mice, Congenic; Mice, Knockout; Motor Activity - genetics; Motor neuron disease; Phenotype; Psychomotor Performance - physiology; Sex Characteristics; Survival Analysis
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2010.06.004

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.