Gene: 1444 | Name: Tgfbr1 | Family: Kinase | Subfamily: Serine/Threonine Kinas... | Accession: D25540 | GI: 483375 |
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Gene
1444
Summary of Phenotypic Analysis
Changes
related to genotype:
There were no significant differences detected in the heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
Weaned progeny from the heterozygous matings were genotyped. No homozygous mutant mice were identified by PCR, whereas wild-type and heterozygous mutant mice were present. The genotypic ratio suggested an embryonic lethal phenotype.
ES cells derived from the 129/OlaHsd mouse substrain were used to generate chimeric mice. F1 mice were generated by breeding with C57BL/6 females. The resultant F1N0 heterozygotes were backcrossed to C57BL/6 mice to generate F1N1 heterozygotes. F2N1 heterozygous mutant mice were produced by intercrossing F1N1 heterozygous males and females.
Wild-type control mice and heterozygous mutant mice were evaluated by the following examinations or tests:
Gene 1444
Behavior
There were no significant differences detected in the heterozygous
mutant animals when compared with age- and gender-matched wild-type control
mice.
Heterozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on seven behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Startle response/PPI test, Tail flick test, Hot plate test, and
Metrazol test.
Mouse
ID numbers are as follows for the N1 generation:
10 heterozygous mutant males (368804, 368807, 368820, 379076, 379077, 379078,
379079, 379080, 379081, 379082)
24 wild-type control males (366281, 368805, 368806, 368809, 368819, 368981,
369533, 370412, 371779, 372236, 373709, 374965, 376410, 377341, 377376, 377403,
377791, 379074, 379942, 379943, 379967, 379969, 381201, 383586)
ES cells derived from the 129/OlaHsd mouse substrain were used to generate
chimeric mice. F1 mice were generated by breeding with C57BL/6 females.
The resultant F1N0 heterozygotes were backcrossed to C57BL/6 mice to generate
F1N1 heterozygotes. F2N1 heterozygous mutant mice were produced by
intercrossing F1N1 heterozygous males and females.
Behavior Findings:
There were no genotype-related or biologically significant differences noted
between heterozygous mutant and wild-type control mice for any of the
parameters evaluated during behavior testing.
Gene 1444
Expression
Summary
Taqman Summary:
The highest levels of RNA transcripts are detectable in lung, liver, thymus,
lymph nodes, skin, gallbladder, urinary bladder, pituitary gland, adrenal
gland, salivary gland, testis, epididymis, seminal vesicle, coagulating gland,
prostate gland, ovary, uterus and white fat.
Moderate levels of RNA transcripts are also detectable in all other tissues analyzed: whole brain, cortex, subcortical region, cerebellum, brainstem, olfactory bulb, spinal cord, eye, Harderian glands, heart, pancreas, kidney, spleen, bone marrow, skeletal muscle, tongue, stomach, small intestine, cecum and colon.
LacZ Summary:
LacZ expression was detected in all organs examined. Most striking
expression was detected in aorta and other blood vessels, heart valve, renal
papilla, muscularis of the urinary bladder, corpus lutea in the ovary and in
testis. Staining was observed in different tissue and cell types,
including neurons, smooth and cardiac muscle, cartilage, epithelium, lymphatic
tissue, adipose tissue and blood vessels.
LacZ expression was detected in: brain, spinal cord, sciatic nerve, eyes, thymus, spleen, lymph nodes, bone marrow, aorta, heart, lung, liver, pancreas, kidney, urinary bladder, thyroid gland, trachea, pituitary gland, adrenal glands, skeletal muscle, skin, testis, prostate gland, ovary, uterus and cervix.
Gene 1444
Densitometry
There were no significant differences detected in the heterozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
The following mice were evaluated by dual-energy x-ray absorptiometry.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 336830)
3 wild-type control males (328754, 328757, 336823)
Bone Mineral Density (BMD in g/cm2 ), fat % (fat percent expressed
as a percentage of body soft tissue compartment), and R-value of soft tissue
were calculated from Bone Mineral Content (BMC in g), bone and tissue areas (cm2 ), and total tissue mass
(g) generated by a PIXImus densitometer.
Densitometric Findings:
Incidental densitometric differences were present between some mice. These findings were considered to represent background differences occasionally seen in this strain of mice, differences due to spontaneous disease, age-related differences, and/or differences of a nonspecific etiology. They were not considered to be genotype related.
Gene 1444
Histopathology
There were no significant differences detected in the heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
Tissues from the following mice were evaluated histologically.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 336830)
3 wild-type control males (328754, 328757, 336823)
No Significant Abnormalities:
The following tissues were examined and considered to have no genotype-related abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral cavity, lymph nodes, aorta, lungs, liver, gallbladder, pancreas, spleen, kidneys, urinary bladder, stomach, small and large intestines, larynx, esophagus, trachea, thyroid gland, thymus gland, tongue, skeletal muscle, sciatic nerve, mammary glands, vertebrae, spinal cord, bone (skull, sternum, femur, tibia, and stifle joint), reproductive tract (including gonads), eyes, Harderian glands, integumentary system (skin and either clitoral or preputial glands), and bone marrow.
Bone
marrow was examined in sections of sternum, vertebrae, and/or femur and tibia.
Marrow cellularity, myeloid:erythroid (M:E) ratio, myeloid and erythroid
maturation sequences, and numbers of megakaryocytes were evaluated.
Incidental lesions were present in some tissues. These findings were
considered to represent background lesions occasionally seen in this strain of
mice, lesions due to spontaneous disease, age-related lesions, and/or lesions
of a nonspecific etiology. They were not considered to be genotype
related.
Gene 1444
Necropsy
There were no significant differences detected in the heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
The following mice were necropsied. Body weight, body length, and organ weights were obtained, and gross pathological findings were recorded.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 336830)
3 wild-type control males (328754, 328757, 336823)
Mice were examined for the following observables: adrenal glands, body length,
body weight, bone marrow, bone - cranium, bone - femur, bone - sternum, bone -
stifle joint, bone - vertebral column, brain, cecum, colon, duodenum,
epididymis - seminal vesicle, esophagus, eyes, gallbladder, general appearance,
Harderian glands, heart, heart weight, ileum, jejunum, kidney weight, kidneys,
liver, liver weight, lungs, lymph nodes, mesentery, ovaries, pancreas, penis,
salivary glands, sciatic nerve, scrotum, skeletal muscle, skin, skinned mouse,
spleen, spleen weight, stomach, testes, testes - epididymis weight, thymus,
thymus weight, tongue, trachea, urinary bladder, urine, uterus, and vagina.
(Gender-specific observables apply to the appropriate gender.)
Necropsy Findings:
There were no genotype-related or biologically significant differences noted between mutant and wild-type control mice for any of the parameters evaluated at necropsy. Incidental lesions were present in some tissues. These findings were considered to represent background lesions occasionally seen in this strain of mice, lesions due to spontaneous disease, age-related lesions, and/or lesions of a nonspecific etiology. They were not considered to be related to genotype.
Body and Organ Weight Findings:
Differences in body length, body weight, organ weights, and/or organ weight to body weight ratios were present between individual mice. The variability between mice usually fell within our historical reference ranges and was not correlated with genotype.
Gene 1444
Clinical Chemistry
There were no significant differences in the heterozygous mutant mice when
compared with age- and gender-matched wild-type control mice.
Serum
samples from the following mice were evaluated by a clinical chemistry panel.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 336830)
3 wild-type control males (328754, 328757, 336823)
Values for the various analytes evaluated were generally similar between
heterozygous mutant and wild-type control mice. Although variations in clinical
chemistry values were present in some mice, they were not related to genotype
and, thus, were not considered phenotypically relevant.
Gene 1444
Hematology
There
were no significant differences in the heterozygous mutant mice when compared
with age- and gender-matched wild-type control mice.
Blood
samples from the following mice were evaluated by a complete blood count and
differential cell count.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 348448)
3 wild-type control males (328754, 328757, 336823)
Although minor variations of hematological values were present in some mice,
these changes were not related to genotype and, thus, were not considered
phenotypically relevant.
Gene 1444
Physical Examination
There
were no significant differences detected in the heterozygous mutant mice when
compared with age- and gender-matched wild-type control mice.
The
following mice were evaluated by physical examination.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (336828, 336829, 336831)
3 heterozygous mutant males (336825, 336826, 336827)
3 wild-type control females (328765, 328767, 336830)
3 wild-type control males (328754, 328757, 336823)
Mice were examined in detail as follows: anus, behavior, body shape, claws,
coat - fur, coat color - back, coat color - belly, ear - left, ear - right, eye
- left, eye - right, eye color - left, eye color - right, feces, forelimb -
left, forelimb - right, forelimb number of amputated digits - left, forelimb
number of amputated digits - right, forelimb number of digits - left, forelimb
number of digits - right, general appearance, genitals - female, genitals -
male, hair type, head shape, hindlimb - left, hindlimb - right, hindlimb number
of amputated digits - left, hindlimb number of amputated digits - right,
hindlimb number of digits - left, hindlimb number of digits - right, injuries,
lesions, limb shape, locomotor, lumps - masses, mammary glands, mice in cage,
respiration, skin appearance, snout, swelling - joints, tail, teeth color,
teeth length, urine, and whiskers. (Gender-specific observables apply to the
appropriate gender.)
Individual
heterozygous mutant mice had only occasional minor differences in observed
physical features compared to wild-type control mice. These findings are
considered to represent individual variability, background features
occasionally seen in this strain of mice, findings due to spontaneous disease,
age-related findings, and/or findings of a nonspecific etiology. However, none
of these differences was regarded as biologically significant or genotype
related.