Amino acid replacement: W213term.
G24946169A
W244term | Nmnat-PA; W244term | Nmnat-PB; W213term | Nmnat-PC; W213term | Nmnat-PD
W213term
G to A nucleotide change at the second or third position of the Trp codon leads to a nonsense mutation (exact site of mutation unspecified). Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.
Flies with eyes that are mostly homozygous for Nmnat2 (due to somatic clones induced using Scer\FRT and Scer\FLP1ey.PN) with heterozygous patches are smooth with a normal external morphology. Electroretinogram (ERG) recordings from such eyes belonging to young mutants show reduced depolarization and on/off responses. Transmission electron microscopy of lamina synapses from 1-day-old flies with these clones reveal morphological defects; the laminae are disorganized, with various numbers of terminals. The terminals contain a fragmented cytoskeleton and misshapen membrane organelles. In presynaptic terminals, the T-bars are amorphous and less electron dense compared to wild type, but they are surrounded by clusters of normally sized synaptic vesicles. However, the size of the T-bar profile, measured by the width of platforms is significantly reduced compared to wild type.
Eyes with Nmnat2 somatic clones show early-onset neuronal degeneration. At 96h after puparium formation (APF), the size of rhabdomeres are reduced with respect to wild type, although the development of photoreceptor terminals is mostly normal. As the mutant photoreceptors age, the number of recognizable terminals per cartridge declines and the active zone structure becomes smaller and amorphous. In 2-day-old mutants, the rhabdomeres are more reduced in size compared to in the 96h APF flies and large vacuoles are abundant in individual ommatidia; by 28 days, the rhabdomeres are barely recognizable. The magnitude of the depolarization and the on/off transients in ERG recordings also decline with age.
Flies with Nmnat2 clones in the eye show a high level of light-induced degeneration. When flies are raised in the dark, at 1 day of age rhabdomere size and photoreceptor terminal morphology is comparable to wild type. In contrast, 1-day-old flies raised in a 12-h light/dark cycle show a dramatic reduction of rhabdomere size. At 10 days of age, dark-reared flies show a much less severe phenotype than those raised in a light/dark cycle, although these flies still exhibit some sign of neurodegeneration, such as small rhabdomeres, the presence of vacuoles in the cell body, and ultrastructural defects in the photoreceptor terminals.
Nmnat2 has rhabdomere | somatic clone phenotype, suppressible | partially by norpAP24
Nmnat2 has ommatidium | somatic clone phenotype, suppressible | partially by norpAP24
Nmnat2 has retina phenotype, non-suppressible by su(rdgA)4040
Nmnat2 has rhabdomere | somatic clone phenotype, non-suppressible by Scer\GAL4GMR.PF/BacA\p35UAS.cHa
Nmnat2 has ommatidium | somatic clone phenotype, non-suppressible by Scer\GAL4GMR.PF/BacA\p35UAS.cHa
Expression of BacA\p35Scer\UAS.cHa under the control of Scer\GAL4GMR.PF in Nmnat2 photoreceptor clones does not suppress the Nmnat2 phenotype.
Selected as: a mutant with abnormal synapse structure in R1-R6 terminals and abnormal ERG responses from an "eyFLP" screen of flies with grossly normal eye morphology that phototax poorly.