Identification of a novel mutant allele of <scp>LIM</scp> homeobox transcription factor 1 alpha (<i>dreher</i>) in mice

• Jun‐ichi Suto

  Institute of Agrobiological Sciences National Agriculture and Food Research Organization (NARO) Tsukuba Japan

抄録

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.

収録刊行物

• Congenital Anomalies

  Congenital Anomalies 62 (1), 18-26, 2021-12

  Wiley

キーワード

• Developmental Biology
• Embryology
• General Medicine
• Pediatrics, Perinatology and Child Health

詳細情報

• CRID: 1360290229196790144
• NII論文ID: 210000159483
• DOI: 10.1111/cga.12450
• ISSN: 17414520
• ISSN: 09143505
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cga.12450
• Web Site: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cga.12450
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