Phenotypes associated with this allele

• Allele Symbol: Tg(Mt1-Hgf)19Lmb
• Allele Name: transgene insertion 19, Glenn Merlino
• Allele ID: MGI:3050880
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Mt1-Hgf)19Lmb/0	involves: 129/Sv * C57BL/6J * FVB/N * SJL	MGI:2653473
cx2	Tg(Dct-Birc5)21Gros/0 Tg(Mt1-Hgf)19Lmb/0	involves: C57BL/6 * CBA * FVB/N	MGI:4353825
tg3	Tg(Mt1-Hgf)19Lmb/0	involves: C57BL/6 * CBA * FVB/N	MGI:4353885
tg4	Tg(Mt1-Hgf)19Lmb/0	involves: C57BL/6 * FVB/N	MGI:5829549
tg5	Tg(Mt1-Hgf)19Lmb/0	involves: FVB/N	MGI:5788591

Genotype
MGI:2653473

cx1

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Tg(Mt1-Hgf)19Lmb/0
• Genetic Background: involves: 129/Sv * C57BL/6J * FVB/N * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

increased tumor incidence ( J:79704 )

• alpha-actin positive neoplasms arise also at ectopic non-skeletal muscle sites, such as cerebellum, pituitary, esophagus, pancreas and stomach

increased rhabdomyosarcoma incidence ( J:79704 )

• mutants develop malignant rhabdomyosarcoma arising from trunk and limb skeletal muscle with high penetrance and short latency

• mean age of onset of 3.3 months

increased melanoma incidence ( J:79704 )

• 2 of 34 mutants develop malignant melanoma

muscle

abnormal myogenesis ( J:79704 )

• myogenic precursors (satellite cells) cultured in fusion media remain poorly differentiated, indicating blocked myogenesis

increased satellite cell number ( J:79704 )

• earlier appearance of hyperplastic satellite cells in skeletal muscle

increased rhabdomyosarcoma incidence ( J:79704 )

• mutants develop malignant rhabdomyosarcoma arising from trunk and limb skeletal muscle with high penetrance and short latency

• mean age of onset of 3.3 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rhabdomyosarcoma		DOID:3247		J:79704

Genotype
MGI:4353825

cx2

• Allelic Composition: Tg(Dct-Birc5)21Gros/0; Tg(Mt1-Hgf)19Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * FVB/N

neoplasm

increased skin tumor incidence ( J:122181 )

• following a single UV exposure, tumor formation is accelerated compared to Tg(MT-HGFSF)19Lmb animals, with a mean onset of formation of 18 weeks

• tumor density is 7.7 lesions/mouse compared to 5.2 in Tg(MT-HGFSF)19Lmb mutants

increased metastatic potential ( J:122181 )

• lymph node metastasis by melanocytic cells is observed in about one third of mice

• significantly higher rates of lung metastasis (53% vs 22%) are detected compared to Tg(MT-HGFSF)19Lmb mice

• prominent involvement of blood vessels and lymphatics in metastasis by melanoma cells is frequently noted

increased melanoma incidence ( J:122181 )

• melanocytic tumors are visible on the skin and histologically, infiltration of large melanized cells is observed

increased incidence of tumors by UV-induction ( J:122181 )

• melanocytes in mice show a predisposition to UV-induced melanocytic tumor formation

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:122181 )

• following a single UV exposure, melanocytes in neonatal skin show significantly reduced sensitivity to UV-induced apoptosis compared to Tg(MT-HGFSF)19Lmb single-mutant mice

• following UV exposure, metastasized melanomas show reduced apoptotic cell numbers compared to non-metastasized melanomas from Tg(MT-HGFSF)19Lmb mice

integument

increased skin tumor incidence ( J:122181 )

• following a single UV exposure, tumor formation is accelerated compared to Tg(MT-HGFSF)19Lmb animals, with a mean onset of formation of 18 weeks

• tumor density is 7.7 lesions/mouse compared to 5.2 in Tg(MT-HGFSF)19Lmb mutants

Genotype
MGI:4353885

tg3

• Allelic Composition: Tg(Mt1-Hgf)19Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * FVB/N

neoplasm

neoplasm ( J:122181 )

N • no mice show metastasis of tumors to the lymph nodes

increased skin tumor incidence ( J:122181 )

• following a single UV exposure, tumors develop with a mean onset of 24 weeks

integument

increased skin tumor incidence ( J:122181 )

• following a single UV exposure, tumors develop with a mean onset of 24 weeks

Genotype
MGI:5829549

tg4

• Allelic Composition: Tg(Mt1-Hgf)19Lmb/0
• Genetic Background: involves: C57BL/6 * FVB/N

pigmentation

abnormal extracutaneous pigmentation ( J:34022 )

• melanosis in and around the meninges throughout the CNS including the brain and in lymph nodes, with increased severity with age

ectopic melanocytes ( J:34022 )

hyperpigmentation ( J:34022 )

• at 8 days of age there are increased melanocytes throughout the dermis and epidermis, skin hyperpigmentation in the extremities, and black abdominal spots

cellular

abnormal melanoblast migration ( J:34022 )

embryo

abnormal melanoblast migration ( J:34022 )

muscle

ectopic skeletal muscle ( J:34022 )

Genotype
MGI:5788591

tg5

• Allelic Composition: Tg(Mt1-Hgf)19Lmb/0
• Genetic Background: involves: FVB/N

muscle

ectopic skeletal muscle ( J:34022 )

• ectopic development of striated muscle in the CNS can be found in paralyzed adults, more frequently in spinal cord than brain

nervous system

abnormal spinal cord ventral horn morphology ( J:50947 )

• paralyzed mice often have cytoarchitectural asymmetry with distorted dorsal and ventral horns

behavior/neurological

hindlimb paralysis ( J:34022 )

• approximately 5% are reported to develop hindlimb paralysis between 4.5 and 6.5 weeks of age

neoplasm

increased metastatic potential ( J:50947 )

• 21% of mice exhibit melanoma metastasis to sites like the liver, lung, pancreas, epididymis, femur, lymph node, and spleen

increased melanoma incidence ( J:50947 )

• 22% of mice 6 months or older develop malignant melanoma

• average age of melanoma onset is 15.6 months

• melanocytic tumors occur predominantly in the skin and subcutaneous areas with heavy population of melanocytes, including the back, neck, tails, and ears, and less frequently in prepuce and the exorbital and mammary glands

• melanocytic tumors arise preferentially in males, with 17 of 19 mice with melanomas being male

• three types of melanomas are seen: epitheloid cell type resembling pigmented melanomas, spindle cell type resembling schwannomas with the Antonini type A pattern, or mixed population with epitheloid and schwannomatous components

increased cutaneous melanoma incidence ( J:50947 )

digestive/alimentary system

intestinal obstruction ( J:34022 )

renal/urinary system

kidney failure ( J:34022 )

mortality/aging

premature death ( J:34022 )

• nearly 80% die by 6 months of age, and causes is usually sporadic intestinal obstruction or progressive renal failure

pigmentation

ectopic melanocytes ( J:50947 )

• melanocytes are inappropriately abundant in the dermis, at the dermal-epidermal junction, and in the basal layer of the epidermis

• melanocytes are most heavily concentrated in the skin of the paws, tails, ears, muzzle and penis and dorsal skin

• many melanocytes are aberrantly localized to the prepuce

integument

increased cutaneous melanoma incidence ( J:50947 )