Nucleotide substitution: G?A. Amino acid replacement: R104H.
G541937A
G?A
R104H | lwr-PA; R104H | lwr-PB; R104H | lwr-PC; R104H | lwr-PD
R104H
hemocyte | increased number (with lwr4-3)
hemocyte | increased number (with lwr14)
lamellocyte | increased number (with lwr14)
Over 90% of lwr4-3/lwr5 and lwr5/lwr14 larvae have melanotic tumours, which are surrounded by lamellocytes. Four days after egg lay, the amount of circulating hemocytes and lamellocytes are significantly higher in these transheterozygotes. Levels of circulating hemocytes continue to increase six days after egg lay in lwr4-3/lwr5 mutants, but do not further increase after eight days. lwr4-3/lwr5 mutants exhibit large hemocytes and a low penetrance of multinucleate hemocytes. There is no significant population of multinucleate hemocytes in lwr5/lwr14 mutants. There is a significant reduction in crystal cells in both lwr14/lwr5 (>20-fold) and lwr4-3/lwr5 (5- to 10-fold) mutants. lwr4-3/lwr5 mutants show a developmental delay and only 25% undergo pupariation on day 8.
lwr5 mutants develop melanotic tumours during the third larval stage, which become particularly large in the posterior half of the body. In some cases, hemocytes can invade self-tissues such as fat body cells. The number of hemocytes in the hemolymph of lwr4-3/lwr5 mutant larvae is significantly higher than in wild type and the number of lamellocytes is increased within the hemocyte pool. Most aggregated hemocytes consist of lamellocytes that are partially to fully melanized. Mitotic analyses of hemocytes show that lamellocytes do not divide in circulation so the excess number must be due to proliferation in the lymph gland. However, plasmatocytes and prohemocytes do divide in circulation in lwr4-3/lwr5 mutants, while no such division occurs in wild type.
lwr5/lwr4-3 has abnormal immune response phenotype, suppressible by cactE10
lwr5/lwr4-3 has melanotic mass phenotype | larval stage phenotype, suppressible | partially by cactE8/cactE10
lwr5/lwr4-3 has melanotic mass phenotype | larval stage phenotype, suppressible | partially by Df(2L)J4/dl1
lwr5/lwr4-3 has melanotic mass phenotype | larval stage phenotype, suppressible | partially by Df(2L)TW119/Dif1
lwr5/lwr4-3 has melanotic mass phenotype | larval stage phenotype, suppressible by Df(2L)TW119/Df(2L)J4
lwr5/lwr4-3 has increased cell number | larval stage phenotype, suppressible by Df(2L)J4/dl1
lwr5/lwr4-3 has increased cell number | larval stage phenotype, suppressible | partially by Df(2L)J4/Dif2
lwr5/lwr[+] is a suppressor of abnormal meiotic cell cycle | female phenotype of nodDTW
cactE10, lwr5/lwr4-3 has lethal | wandering third instar larval stage phenotype
lwr5/lwr4-3, spz4 has lethal | wandering third instar larval stage phenotype
lwr5/lwr4-3 has embryonic/larval fat body phenotype, suppressible by cactE10
lwr5/lwr4-3 has embryonic/larval hemocoel phenotype, suppressible by cactE10
lwr5/lwr4-3 has hemocyte | increased number phenotype, suppressible by Df(2L)TW119/Df(2L)J4
lwr5/lwr4-3 has hemocyte | increased number phenotype, suppressible | partially by Df(2L)TW119/Dif1
lwr5/lwr4-3 has embryonic/larval hemocyte | increased number phenotype, suppressible | partially by Df(2L)J4/dl1
lwr5/lwr4-3 has lamellocyte | increased number phenotype, suppressible by Df(2L)TW119/Df(2L)J4
lwr5/lwr4-3 has lamellocyte | increased number phenotype, suppressible by Df(2L)J4/Dif2
lwr5/lwr4-3 has embryonic/larval hemocyte | increased number phenotype, suppressible by Df(2L)TW119/Df(2L)J4
lwr5/lwr4-3 has embryonic/larval hemocyte | increased number phenotype, suppressible | partially by Df(2L)J4/Dif2
lwr5/lwr4-3 has embryonic/larval plasmatocyte | increased number phenotype, suppressible | partially by Df(2L)J4/Dif2
lwr5/lwr4-3 has embryonic/larval plasmatocyte | increased number phenotype, suppressible | partially by Df(2L)J4/dl1
lwr5/lwr4-3 has lamellocyte | increased number phenotype, non-suppressible by Df(2L)TW119/Dif1
lwr5/lwr4-3 has lamellocyte | increased number phenotype, non-suppressible by cactE8/cactE10
lwr5/lwr4-3 has lamellocyte | increased number phenotype, non-suppressible by Df(2L)J4/dl1
The penetrance of melanotic tumours is reduced from over 90% in lwr4-3/lwr5 mutants to less than 2% in lwr4-3 Df(2L)TW119/lwr5 Df(2L)J4 triple mutants. The amount of circulating hemocytes and lamellocytes are reduced by day 8 in lwr4-3 Df(2L)TW119/lwr5 Df(2L)J4 triple mutants compared to lwr4-3/lwr5 single mutants. The melanotic tumour penetrance and circulating hemocyte levels are reduced in lwr4-3 Df(2L)J4/lwr5 dl1 and lwr4-3 Df(2L)TW119/lwr5 Dif1 double mutants, but to a lower extent than in lwr4-3 Df(2L)TW119/lwr5 Df(2L)J4 triple mutants. However, the amount of lamellocytes is not reduced in the double mutants. The melanotic tumour penetrance is reduced in lwr4-3 cactE8/lwr5 cactE10 double mutants compared to lwr4-3/lwr5 single mutants and by day 8, the amount of circulating hemocytes is reduced in the double mutants. In contrast, the amount of lamellocytes remains as high as in the single mutants.
In lwr4-3/lwr5; dl1/Df(2L)J4, total numbers of hemocytes are reduced compared to lwr4-3/lwr5 single mutants. Plasmatocyte levels are reduced by 50% compared to single mutants, while lamellocyte levels are not significantly reduced. In lwr4-3/lwr5; Dif2/Df(2L)J4 double mutants the number of lamellocytes are the same as in wild-type larvae, while the number of plasmatocytes are reduced compared to lwr4-3/lwr5 single mutants, but remain higher than in wild type. In lwr4-3/lwr5; Df(2L)TW119/Df(2L)J4 double mutants, the total number of hemocytes, including lamellocytes, is the same as wild type.
lwr5/lwr4-3 is rescued by Scer\GAL476B/lwrUAS.cAa
lwr5/lwr4-3 is partially rescued by lwrUAS.cAa/Scer\GAL4Cg.PA
lwr5/lwr4-3 is partially rescued by Scer\GAL4nanos.PG/lwrUAS.cAa
lwr5/lwr4-3 is partially rescued by lwrUAS.cAa/Scer\GAL4e22c
lwr5 is not rescued by lwrUAS.cAa/Scer\GAL4e22c
lwr5 is not rescued by Scer\GAL4nanos.PG/lwrUAS.cAa
Expression of lwrScer\UAS.cAa in a subset of the lymph gland cells under the control of Scer\GAL476B significantly reduced the infiltration index in lwr4-3/lwr5 mutants, indicating an anti-inflammatory role for lwr.
Expression of lwrScer\UAS.cAa under the control of Scer\GAL4Cg.PA partially rescues the developmental delay of lwr4-3/lwr5 mutants, increasing the amount of animals undergoing pupariation from 25 to 61% at day 8. However, there is no clear rescue of the melanotic tumour phenotype.
lwrScer\UAS.cAa rescues lwr4-3/lwr5 females to adulthood when expressed using Scer\GAL4e22c or Scer\GAL4nos.PG, however the rescued flies are sterile. The ovaries develop to stage 8 or 9 (Scer\GAL4nos.PG) or stage 2 (Scer\GAL4e22c).