Phenotypes associated with this allele

• Allele Symbol: Tardbp^tm1.1Pcw
• Allele Name: targeted mutation 1.1, Philip C Wong
• Allele ID: MGI:4834273
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tardbp^tm1.1Pcw/Tardbp^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4834589
cn2	Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4834592
cn3	Gt(ROSA)26Sor^tm1(cre/ERT)Nat/Gt(ROSA)26Sor^+ Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw	involves: 129 * C57BL/6 * SJL	MGI:4834587
cn4	Gt(ROSA)26Sor^tm1(cre/ERT)Nat/Gt(ROSA)26Sor^+ Tardbp^tm1.1Pcw/Tardbp^+	involves: 129 * C57BL/6 * SJL	MGI:4834588
cn5	Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * FVB/NJ * SJL	MGI:7266812

Genotype
MGI:4834589

cn1

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

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

growth/size/body

decreased body weight ( J:164406 )

• after cre induction by tamoxifen, mice show decrease in body weight relative to controls

adipose tissue

abnormal brown fat cell morphology ( J:164406 )

• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected

abnormal white fat cell morphology ( J:164406 )

• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected

Genotype
MGI:4834592

cn2

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

growth/size/body

decreased body weight ( J:164406 )

• after cre induction by tamoxifen, mice show decrease in body relative to controls

cellular

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes

adipose tissue

decreased total body fat amount ( J:164406 )

• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice

• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass

abnormal brown fat cell morphology ( J:164406 )

• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected

• adipocytes are present in brown fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen

decreased mesenteric fat pad weight ( J:164406 )

• dramatic fat loss is observed

abnormal white adipose tissue morphology ( J:164406 )

abnormal white fat cell morphology ( J:164406 )

• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected

• adipocytes are present in white fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen

homeostasis/metabolism

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes

Genotype
MGI:4834587

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺; Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

abnormal survival ( J:164406 )

• when cre expression is induced with a tamoxifen-containing diet (400 mg/kg of chow), mice die by day 9 post-introduction of tamoxifen

growth/size/body

decreased body weight ( J:164406 )

• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not

weight loss ( J:164406 )

• mice show a cumulative loss of body weight compared to controls following cre induction, but energy intake (cumulative food intake) is similar to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:164406 )

N • without induction of cre by tamoxifen treatment, animals are indistinguishable from controls

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after induction is basis for increased weight loss

abnormal respiratory quotient ( J:164406 )

• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6

adipose tissue

decreased total body fat amount ( J:164406 )

• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice

• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass

cellular

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after induction is basis for increased weight loss

behavior/neurological

abnormal food intake ( J:164406 )

• energy intake on day 7 is significantly higher than on day 1 after cre induction

Genotype
MGI:4834588

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺; Tardbp^tm1.1Pcw/Tardbp⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

growth/size/body

decreased body weight ( J:164406 )

• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not

homeostasis/metabolism

abnormal respiratory quotient ( J:164406 )

• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6

adipose tissue

decreased total body fat amount ( J:164406 )

• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice

• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass

Genotype
MGI:7266812

cn5

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * FVB/NJ * SJL

reproductive system

teratozoospermia ( J:324061 )

♂ • most cauda epididymal sperm are morphologically abnormal

abnormal sperm flagellum morphology ( J:324061 )

♂ • ~55% of sperm tails are curved/bent

abnormal sperm head morphology ( J:324061 )

♂ • roughly 50% of cauda sperm show deformed or detached heads

♂ • ~55% of sperm show head and midpiece bent over the principal piece of the tail

absent sperm head ( J:324061 )

♂ • headless sperm are observed

decreased male germ cell number ( J:324061 )

♂ • extensive male germ cell depletion is observed at P35

♂ • germ cell depletion is progressively worse at 3, 7, and 21 months of age

oligozoospermia ( J:324061 )

♂ • males exhibit 7.4 times less cauda epididymal sperm than control males

abnormal chromosomal synapsis ( J:324061 )

♂ • diplotene-like spermatocytes display nonhomologous chromosome synapsis

♂ • zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes

♂ • pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks

increased male germ cell apoptosis ( J:324061 )

♂ • TUNEL staining showed a significant increase in spermatocyte apoptosis

abnormal seminiferous tubule epithelium morphology ( J:324061 )

♂ • vacuole formation is observed within the seminiferous epithelium at P35

♂ • at advanced ages, the seminiferous epithelium only consists of Sertoli cells

♂ • onset of seminiferous epithelium pathology with reduced cellularity is at P12

small seminiferous tubules ( J:324061 )

♂ • at P35, the seminiferous tubule diameter appears narrower than in control males

♂ • a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age

seminiferous tubule degeneration ( J:324061 )

♂ • atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35

♂ • vacuole formation is progressively worse at 3, 7, and 21 months of age

small testis ( J:324061 )

♂ • testis size is severely decreased at P35

decreased testis weight ( J:324061 )

♂ • a 2.9-fold reduction in testis weight is seen at 3 months of age

arrest of spermatogenesis ( J:324061 )

♂ • at P35, spermatogonia and a few meiotic cells can be seen but no round spermatids are detected

♂ • at 3-4 months of age, flow cytometry data showed a significant decrease in 1N cells (round spermatids) and an increase in 2N (spermatogonia, Sertoli, peritubular, and Leydig cells) and 4N (primary spermatocytes) cells, indicating arrest in meiosis

arrest of male meiosis ( J:324061 )

♂ • spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage

reduced male fertility ( J:324061 )

♂ • 3-month-old males are severely subfertile, producing a significantly lower number of litters than control males over a 6-month period (0.6 litters versus 6 litters, respectively)

cellular

teratozoospermia ( J:324061 )

♂ • most cauda epididymal sperm are morphologically abnormal

abnormal sperm flagellum morphology ( J:324061 )

♂ • ~55% of sperm tails are curved/bent

abnormal sperm head morphology ( J:324061 )

♂ • roughly 50% of cauda sperm show deformed or detached heads

♂ • ~55% of sperm show head and midpiece bent over the principal piece of the tail

absent sperm head ( J:324061 )

♂ • headless sperm are observed

decreased male germ cell number ( J:324061 )

♂ • extensive male germ cell depletion is observed at P35

♂ • germ cell depletion is progressively worse at 3, 7, and 21 months of age

oligozoospermia ( J:324061 )

♂ • males exhibit 7.4 times less cauda epididymal sperm than control males

abnormal chromosome morphology ( J:324061 )

♂ • zygotene-like spermatocytes show short chromosome length and abnormal number of chromosomes

♂ • some pachytene-like spermatocytes show abnormally long chromosomes

abnormal chromosome number ( J:324061 )

♂ • zygotene-like spermatocytes show abnormal number of chromosomes likely due to abnormal synapsis between nonhomologous chromosomes

abnormal chromosomal synapsis ( J:324061 )

♂ • diplotene-like spermatocytes display nonhomologous chromosome synapsis

♂ • zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes

♂ • pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks

arrest of male meiosis ( J:324061 )

♂ • spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage

increased male germ cell apoptosis ( J:324061 )

♂ • TUNEL staining showed a significant increase in spermatocyte apoptosis

abnormal double-strand DNA break repair ( J:324061 )

♂ • pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:324061 )

♂ • vacuole formation is observed within the seminiferous epithelium at P35

♂ • at advanced ages, the seminiferous epithelium only consists of Sertoli cells

♂ • onset of seminiferous epithelium pathology with reduced cellularity is at P12

small seminiferous tubules ( J:324061 )

♂ • at P35, the seminiferous tubule diameter appears narrower than in control males

♂ • a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age

seminiferous tubule degeneration ( J:324061 )

♂ • atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35

♂ • vacuole formation is progressively worse at 3, 7, and 21 months of age

small testis ( J:324061 )

♂ • testis size is severely decreased at P35

decreased testis weight ( J:324061 )

♂ • a 2.9-fold reduction in testis weight is seen at 3 months of age

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:324061 )

♂ • pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair