Identification of a novel mutant allele of LIM homeobox transcription factor 1 alpha (dreher) in mice.

Autor: Suto JI; Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, Japan.
Jazyk: angličtina
Zdroj: Congenital anomalies [Congenit Anom (Kyoto)] 2022 Jan; Vol. 62 (1), pp. 18-26. Date of Electronic Publication: 2021 Dec 01.
DOI: 10.1111/cga.12450
Abstrakt: A male mouse exhibiting bidirectional circling behavior was identified in a Y-chromosome consomic strain known as DH-Chr Y RR . The putative mutation responsible for the circling behavior was inherited in an autosomal recessive manner and was termed circ. To identify its causative gene, we performed exome sequencing; of the 34 candidates discovered, we found a novel nonsynonymous single nucleotide variation in LIM homeobox transcription factor 1 alpha (Lmx1a) (c.394G > C, p.Gly132Arg). The genetic linkage between Lmx1a and circ was confirmed in (♀BALB/cA × ♂DH-Chr Y RR -circ/circ) F 2 and (♀C57BL/6J × ♂DH-Chr Y RR -circ/circ) F 2 mice. The Lmx1a mutation led to many abnormalities that affected growth, pigmentation, reproduction, and cerebellar morphology. We showed that (♀BALB/cA × ♂DH-Chr Y RR -circ/circ) F 2 -circ/circ mice demonstrated significantly lower body mass than the F 2 -+/? mice. Unlike the F 2 -+/? mice, few (♀C57BL/6J × ♂DH-Chr Y RR -circ/circ) F 2 -circ/circ mice exhibited a belly spot. The circ/circ females were also invariably sterile, probably because of an underdeveloped uterus. Moreover, the circ/circ mice presented fewer cerebellar granule cells with lower density than the F 2 -+/? mice. Although non-complementation between circ and the known Lmx1a mutant alleles remains unconfirmed, the coisogenic nature of circ strongly suggests that it is a novel variant of Lmx1a, previously known as dreher. Therefore, we have assigned the gene symbol Lmx1a dr-circ to circ. In addition to Lmx1a dr-J and Lmx1a dr-kjmi , Lmx1a dr-circ is the third allele that causes a missense mutation within LIM domains. Identification of missense mutations is necessary to specify the critical residues for abrogating the in vivo functions of LMX1A.
(© 2021 Japanese Teratology Society.)
Databáze: MEDLINE
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