title: Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice.
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.
authors.affiliation: Neurodegenerative Diseases Research Centre, Tokai University Graduate School of Medicine, Isehara, Kanagawa 259-1193, Japan. shinji@is.icc.u-tokai.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Hadano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshii
authors.forename: Asako
authors.initials: A
authors.lastname: Otomo
authors.forename: Ryota
authors.initials: R
authors.lastname: Kunita
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki-Utsunomiya
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Joh-E
authors.initials: JE
authors.lastname: Ikeda
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency*; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D011597:Psychomotor Performance / Q000502:physiology; D012727:Sex Characteristics; D016019:Survival Analysis
chemical_list: C512358:Als2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors