| First Author | Suto JI | Year | 2022 |
| Journal | Congenit Anom (Kyoto) | Volume | 62 |
| Issue | 1 | Pages | 18-26 |
| PubMed ID | 34816488 | Mgi Jnum | J:324869 |
| Mgi Id | MGI:6852609 | Doi | 10.1111/cga.12450 |
| Citation | Suto JI (2022) Identification of a novel mutant allele of LIM homeobox transcription factor 1 alpha (dreher) in mice. Congenit Anom (Kyoto) 62(1):18-26 |
| abstractText | 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 (female symbolBALB/cA x male symbolDH-Chr Y(RR) -circ/circ) F2 and (female symbolC57BL/6J x male symbolDH-Chr Y(RR) -circ/circ) F2 mice. The Lmx1a mutation led to many abnormalities that affected growth, pigmentation, reproduction, and cerebellar morphology. We showed that (female symbolBALB/cA x male symbolDH-Chr Y(RR) -circ/circ) F2 -circ/circ mice demonstrated significantly lower body mass than the F2 -+/? mice. Unlike the F2 -+/? mice, few (female symbolC57BL/6J x male symbolDH-Chr Y(RR) -circ/circ) F2 -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 F2 -+/? 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. |
