Phenotypes associated with this allele

• Allele Symbol: Trpm7^tm1Clph
• Allele Name: targeted mutation 1, David E Clapham
• Allele ID: MGI:3814705
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Trpm7^tm1Clph/Trpm7^tm1Clph Tg(Hoxb7-cre)5526Cmb/0	involves: 129S4/SvJae	MGI:6220897
cn2	Trpm7^tm1Clph/Trpm7^tm1Clph Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:6220878
cn3	Trpm7^tm1Clph/Trpm7^tm1.1Clph Tg(Lck-cre)548Jxm/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:3814863
cn4	Trpm7^tm1Clph/Trpm7^tm1.1Clph Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:3814711
cn5	Trpm7^tm1Clph/Trpm7^tm1Clph Tg(Pax3-cre)1Joe/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:6220898
cn6	Trpm7^tm1Clph/Trpm7^tm1Clph Tg(Nes-cre)1Kln/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:6220891
cn7	Trpm7^tm1Clph/Trpm7^tm1.1Clph Tg(Gata1-cre)1Sho/0	involves: 129S4/SvJae * CD-1	MGI:3814709

Genotype
MGI:6220897

cn1

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1Clph; Tg(Hoxb7-cre)5526Cmb/0
• Genetic Background: involves: 129S4/SvJae

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

renal/urinary system

renal/urinary system phenotype ( J:181963 )

N • at P12, mice exhibit normal kidney size and histology relative to control mice, suggesting normal kidney development

Genotype
MGI:6220878

cn2

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1Clph; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

Representative images of grossly deformed, nonviable Trpm7^tm1Clph/Trpm7^tm1Clph Tg(CAG-cre/Esr1*)5Amc/0 embryos at E9.5 and E10.5

mortality/aging

embryonic lethality, complete penetrance ( J:181963 )

• when a single tamoxifen dose (25 ug/g of body weight) is injected into pregnant females at early gestation stages (E7-E9), all embryos die within 48-72 hrs of treatment

embryo

abnormal developmental patterning ( J:181963 )

• following tamoxifen injection at E7-E9, dying embryos exhibit abnormal body patterning

abnormal embryo morphology ( J:181963 )

• following tamoxifen injection at E7-E9, non-viable embryos are grossly deformed at E9.5 and E10.5

normal phenotype

no abnormal phenotype detected ( J:181963 )

• following a single tamoxifen injection (25 ug/g of body weight) at E14.5, live pups are born in normal ratios, with no dead embryos found in utero 48 hrs after injection

• a single tamoxifen injection (50 ug/g of body weight) into 6-wk-old mice results in normal survival with grossly normal adult mice at 1-2 months after injection

• following 3 daily tamoxifen injections (25-50 ug/g of body weight) into 4-wk-old mice, all adult mice show normal kidney, heart, and liver histology at 4 weeks after injection

Genotype
MGI:3814863

cn3

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1.1Clph; Tg(Lck-cre)548Jxm/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

immune system

abnormal thymus morphology ( J:140630 )

• 85% penetrance of thymic abnormalities

• CD3+ T cells are found distributed throughout the thymus

abnormal thymus cell ratio ( J:140630 )

• increase in the percentage and number of double negative T cells

• increase in the percentage of cells in the DN3 stage

abnormal thymus corticomedullary boundary morphology ( J:140630 )

• the boundary between the cortical and medullary regions is not well defined

abnormal thymus medulla morphology ( J:140630 )

• progressive loss of thymic medullary cells

decreased thymocyte number ( J:140630 )

• substantial reduction in the number of thymocytes

abnormal T cell differentiation ( J:140630 )

• partial block in the transition from double negative to double positive T cells

• block appears to be at the DN3 to DN4 transition as a significant proportion of cells fail to down regulate CD25

decreased T cell number ( J:140630 )

• slight decrease in the percentage and number of T cells in the spleen and lymph nodes but not in the intestine

abnormal T cell physiology ( J:140630 )

• thymocytes lack Mg2+ inhibitable current

• however, Mg2+ influx into freshly isolated T cells is unaffected

hematopoietic system

abnormal thymus morphology ( J:140630 )

• 85% penetrance of thymic abnormalities

• CD3+ T cells are found distributed throughout the thymus

abnormal thymus cell ratio ( J:140630 )

• increase in the percentage and number of double negative T cells

• increase in the percentage of cells in the DN3 stage

abnormal thymus corticomedullary boundary morphology ( J:140630 )

• the boundary between the cortical and medullary regions is not well defined

abnormal thymus medulla morphology ( J:140630 )

• progressive loss of thymic medullary cells

decreased thymocyte number ( J:140630 )

• substantial reduction in the number of thymocytes

abnormal T cell differentiation ( J:140630 )

• partial block in the transition from double negative to double positive T cells

• block appears to be at the DN3 to DN4 transition as a significant proportion of cells fail to down regulate CD25

decreased T cell number ( J:140630 )

• slight decrease in the percentage and number of T cells in the spleen and lymph nodes but not in the intestine

abnormal T cell physiology ( J:140630 )

• thymocytes lack Mg2+ inhibitable current

• however, Mg2+ influx into freshly isolated T cells is unaffected

endocrine/exocrine glands

abnormal thymus morphology ( J:140630 )

• 85% penetrance of thymic abnormalities

• CD3+ T cells are found distributed throughout the thymus

abnormal thymus cell ratio ( J:140630 )

• increase in the percentage and number of double negative T cells

• increase in the percentage of cells in the DN3 stage

abnormal thymus corticomedullary boundary morphology ( J:140630 )

• the boundary between the cortical and medullary regions is not well defined

abnormal thymus medulla morphology ( J:140630 )

• progressive loss of thymic medullary cells

decreased thymocyte number ( J:140630 )

• substantial reduction in the number of thymocytes

Genotype
MGI:3814711

cn4

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1.1Clph; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

mortality/aging

embryonic lethality, complete penetrance ( J:140630 )

• no viable embryos were found, no time of lethality was provided

Genotype
MGI:6220898

cn5

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1Clph; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

Small kidney, kidney cysts, and reduced number of glomeruli in Trpm7^tm1Clph/Trpm7^tm1Clph Tg(Pax3-cre)1Joe/0 mice

renal/urinary system

kidney cyst ( J:181963 )

• at P12, many large renal cysts are observed, unlike in control kidneys

• small cysts first emerge at P4; no cysts are observed at P2

kidney cortex cyst ( J:181963 )

• proximal tubular cysts emerge at P4

• no cysts associated with connecting tubules, distal convoluted tubules, or collecting ducts are observed

decreased renal glomerulus number ( J:181963 )

• at E18.5 and P12, very few glomeruli are observed, unlike in control kidneys

abnormal kidney development ( J:181963 )

small kidney ( J:181963 )

• at E14.5 and E18.5, kidneys are smaller than those of controls

• at P12, kidneys are less than half the size of control kidneys

abnormal nephron morphogenesis ( J:181963 )

• at E14.5, only spherical renal vesicles are present while comma- and S-shaped bodies are clearly absent, unlike in control kidneys

abnormal S-shaped body morphology ( J:181963 )

• at E14.5, S-shaped bodies are absent

abnormal comma shaped body morphology ( J:181963 )

• at E14.5, comma-shaped bodies are absent

abnormal renal tubule morphology ( J:181963 )

• at P2, eosinophilic acellulal material consistent with protein is present in the lumen of dilated renal tubules and the basement membrane is disrupted around dilated tubules

dilated renal tubule ( J:181963 )

• at P2, dilated tubules are observed in the renal cortex, unlike in control kidneys

kidney failure ( J:181963 )

• mice exhibit progressive kidney failure

pigmentation

abnormal hair follicle melanocyte morphology ( J:181963 )

• at P12, dorsal skin shows absence of pigment cells in hair follicles only in the lower trunk region

• at P2, dopachrome tautomerase (DCT)-positive pigment cells in hair follicles are reduced only in the lower trunk

absent hair follicle melanin granules ( J:181963 )

• at P2, pigment in hair follicles is reduced only in the lower trunk

abnormal rostrocaudal coat patterning ( J:181963 )

• at P12, mice exhibit normal agouti fur in the upper trunk but white fur in the lower trunk, unlike control mice

decreased melanocyte number ( J:181963 )

• toluidine blue staining of P2 dorsal lumbar skin sections shows loss of pigment cells in the lower trunk relative to wild-type controls

• immunohistochemistry of P2 dorsal lumbar skin sections confirmed drastic loss of microphthalmia-associated transcription factor (MiTF)-positive or DCT-positive pigment cells in the lower trunk

hypopigmentation ( J:181963 )

• at P2 and P12, mice exhibit loss of pigmentation only in the lower trunk

integument

abnormal hair follicle melanocyte morphology ( J:181963 )

• at P12, dorsal skin shows absence of pigment cells in hair follicles only in the lower trunk region

• at P2, dopachrome tautomerase (DCT)-positive pigment cells in hair follicles are reduced only in the lower trunk

absent hair follicle melanin granules ( J:181963 )

• at P2, pigment in hair follicles is reduced only in the lower trunk

abnormal rostrocaudal coat patterning ( J:181963 )

• at P12, mice exhibit normal agouti fur in the upper trunk but white fur in the lower trunk, unlike control mice

behavior/neurological

impaired limb coordination ( J:181963 )

• mice drag their hind legs in a kneeling posture

hindlimb paralysis ( J:181963 )

• hind legs are paralyzed

• however, forelimbs appear normal

paresis ( J:181963 )

• at P2 and P12, mice exhibit paresis of only the hind legs

nervous system

decreased sensory neuron number ( J:181963 )

• at P2, lumbar DRG shows loss of large-diameter DRG sensory neurons

small dorsal root ganglion ( J:181963 )

• at E18.5, lumbar dorsal root ganglion (DRG) shows normal gray/white matter distributions but smaller cross-sectional areas

growth/size/body

kidney cyst ( J:181963 )

• at P12, many large renal cysts are observed, unlike in control kidneys

• small cysts first emerge at P4; no cysts are observed at P2

kidney cortex cyst ( J:181963 )

• proximal tubular cysts emerge at P4

• no cysts associated with connecting tubules, distal convoluted tubules, or collecting ducts are observed

Genotype
MGI:6220891

cn6

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1Clph; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:181963 )

• mice are born in normal Mendelian ratios and survive to adulthood with no differences in overall appearance, size, fertility or behavior relative to control mice

• brain histology is normal at 12 weeks of age, suggesting that late disruption of brain-specific Trpm7 after E10.5 does not affect brain development

Genotype
MGI:3814709

cn7

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1.1Clph; Tg(Gata1-cre)1Sho/0
• Genetic Background: involves: 129S4/SvJae * CD-1

mortality/aging

embryonic lethality, complete penetrance ( J:140630 )

• no viable embryos were found, no time of lethality was provided