Transgenic analysis of the physiological functions of Mahogunin Ring Finger-1 isoforms.
Mahogunin Ring Finger-1 (Mgrn1) null mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, abnormal head shape, reduced viability, and adult-onset spongiform neurodegeneration. Mgrn1 encodes a highly conserved E3 ubiquitin ligase with four different isoforms which are differentially expressed and predicted to localize to different subcellular compartments. To test whether loss of specific isoforms causes different aspects of the mutant phenotype, we generated transgenes for each isoform and bred them onto the null mutant background. Mice expressing only isoform I or III appeared completely normal. Isoform II rescued or partially rescued the mutant phenotypes, whereas isoform IV had little or no effect. Our data show that different Mgrn1 isoforms are not functionally equivalent in vivo and that the presence of only isoform I or III is sufficient for normal development, pigmentation, and neuronal integrity.
Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA.
Jian
J
Jiao
Hae Young
HY
Kim
Roy R
RR
Liu
Carolyn A
CA
Hogan
Kaihua
K
Sun
Lori Mon
LM
Tam
Teresa M
TM
Gunn
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D002490:Central Nervous System / Q000254:growth & development; D017931:DNA Primers; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D012880:Skin Pigmentation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D020033:Protein Isoforms; C470689:Mgrn1 protein, mouse; D044767:Ubiquitin-Protein Ligases