| Gene: 268 | Name: Twg-pending | Family: Growth Factor | Subfamily: Twisted | Accession: AF292033 | GI: 9837569 |
|---|
Gene 268
Summary of Phenotypic Analysis
Changes related to genotype:
ES
cells derived from the 129/SvJ x 129/Sv-CP mouse substrain were used to
generate chimeric mice. F1 mice were generated by breeding with C57BL/6
females. F2 homozygous mutant mice were produced by intercrossing F1
heterozygous males and females.
Wild-type
control mice, as well as homozygous mutant and heterozygous mutant mice,
were evaluated by the following examinations or tests:
When compared to age- and gender-matched wild-type control mice, homozygous mutant mice frequently had kinky tails at 49 days of age, and infrequently at 300 days of age. Body length was short and body weight was low in homozygous mutant males at 300 days of age. Aging metrics showed trends for short body length, low body weight, and low body weight / body length ratio in homozygous mutant males and, to a lesser degree, in homozygous mutant females at 49, 90, 180, and 300 days of age.
Gene 268
Behavior
Changes related to genotype:
There were no significant differences detected in the
homozygous mutant animals when compared with age- and gender-matched wild-type
control mice.
Homozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on six behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Hot plate test, Startle/PPI, and Metrazol test.
Mouse
ID numbers are as follows:
10
homozygous mutant males (68299, 51253, 68298, 59521, 68295, 51314, 68305,
68307, 68296, 59725)
10 wild-type control males (68300, 59518, 68311, 68297, 71660, 65748, 59723,
59724, 68303, 71657)
ES
cells derived from the 129/SvJ x 129/Sv-CP 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 homozygous mutant mice were produced by
intercrossing F1N1 heterozygous males and females.
Behavior Findings:
There were no genotype-related or biologically significant differences noted
between homozygous mutant and wild-type control mice for any of the parameters
evaluated during behavior testing.
Gene 268
Fertility
Both homozygous males and females were fertile. Their progeny were viable until
weaning, which suggests no abnormalities in the ability of the mutant females
to nurture their pups.
Two to three homozygous mutant mice of each gender were set up in a fertility
mating with a wild-type mate at seven to eight weeks of age. The numbers of
pups born from one to three litters were recorded. Three weeks later, the live
pups were counted and weaned.
Mouse ID numbers are as follows:
3 homozygous mutant males (10827, 28909, 50962)
2 homozygous mutant females (9138, 28906)
Gene 268
Expression
Summary
RT-PCR Summary:
RNA transcripts are detectable in all tissues analyzed: brain, cortex, subcortical
region, cerebellum, brainstem, olfactory bulb, eye, heart, lung, liver,
pancreas, kidneys, spleen, thymus, lymph nodes, bone marrow, skin, gallbladder,
urinary bladder, pituitary gland, adrenal gland, salivary gland, skeletal
muscle, tongue, stomach, small intestine, large intestine, cecum, testis,
epididymis, seminal vesicle, coagulating gland, prostate gland, ovary and
uterus.
Gene 268
Histopathology
There were no significant differences detected in the homozygous mutant and
heterozygous mutant animals when compared with age- and gender-matched
wild-type control mice.
The following mice were evaluated by histopathological examination.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (10796, 10799, 10802)
3 homozygous mutant males (10828, 10829, 10834)
1 heterozygous mutant female (10801)
1 heterozygous mutant male (10832)
1 wild-type control female (10798)
1 wild-type control male (10833)
300 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (10699, 10702, 11656, 13263)
5 homozygous mutant males (10827, 11655, 11657, 11658, 15612)
3 wild-type control females (10701, 13264, 51411)
3 wild-type control males (11212, 14152, 15084)
No Significant Abnormalities:
Tissues examined and considered to have no genotypically significant
abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral
cavity, lymph nodes, aorta, lungs, 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 evaluated in sections of sternum, vertebrae, and/or femur and
tibia. Marrow cellularity, numbers of megakaryocytes, and myeloid:erythroid
(M:E) ratio are within normal limits. Myeloid and erythroid precursors show a
normal maturation sequence.
Incidental lesions were present in some tissues, including Harderian gland
adenomas in 2 homozygous mutant mice (female 13263, male 15612) and a cystic
bulbourethral gland in a homozygous mutant male (10827). These findings are
considered to represent background lesions occasionally seen in this strain of
mice, lesions due to spontaneous disease, age-related lesions, lesions due
to procedural artifacts, and/or lesions of a nonspecific etiology. They
are not considered to be genotype related.
Gene 268
Necropsy
Changes
related to genotype:
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:
5 homozygous mutant females (10799, 10802, 16040, 16042, 17646)
6 homozygous mutant males (10828, 10829, 10834, 18210, 19478,19479)
2 heterozygous mutant females (10801, 16041)
2 heterozygous mutant males (10832, 18208)
3 wild-type control females (10798, 17458, 17459)
3 wild-type control males (10833, 18211, 19425)
300
Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (10699, 10702, 11656, 13263)
5 homozygous mutant males (10827, 11655, 11657, 11658, 15612)
3 wild-type control females (10701, 13264, 51411)
3 wild-type control males (11212, 14152, 15084)
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, including a
mass from the inguinal region in a homozygous mutant male (10827) that was a
cystic bulbourethral gland histologically. These findings were considered
to represent background lesions occasionally seen in this strain of mice,
lesions due to spontaneous disease, age-related lesions, lesions due to
procedural artifacts, and/or lesions of a nonspecific etiology. They were
not considered to be related to genotype.
Body
and Organ Weight Findings:
When compared to age- and gender-matched wild-type control mice in the 300 day cohort, body length was short and body weight was low for 4 of 5 homozygous mutant males (10827, 11655, 11658, 15612). These differences were regarded as related to genotype. Other 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 for these differences usually fell within our historical reference ranges and was not correlated with genotype.
Gene 268
Clinical
Chemistry
There were no significant differences detected in the homozygous mutant and
heterozygous mutant animals when compared with age- and gender-matched
wild-type control mice.
Serum samples from the following mice were evaluated by a clinical biochemistry
panel. The data were compiled from N0F2 and N1F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (16042, 77285, 83340)
3 homozygous mutant males (74894, 75995, 78632)
1 heterozygous mutant female (77655)
1 heterozygous mutant male (78633)
2 wild-type control females (74907, 83338)
2 wild-type control males (74896, 74902)
90 Day Cohort Mouse ID numbers are as follows:
1 homozygous mutant female (14157)
4 homozygous mutant males (14151, 14153, 14155, 46975)
2 wild-type control females (14159, 14934)
1 wild-type control male (14152)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (13263, 14157, 14935, 15078)
4 homozygous mutant males (14151, 14153, 15612, 46975)
4 wild-type control females (13264, 14159, 14934, 15081)
3 wild-type control males (14152, 15082, 15084)
300-360 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (13263, 50952, 50954, 51412)
4 homozygous mutant males (10827, 11655, 11657, 15612)
4 wild-type control females (13264, 51409, 51411, 57775)
3 wild-type control males (11212, 14152, 57781)
Values for the various analytes evaluated were generally similar between
homozygous mutant, heterozygous mutant, and wild-type control mice. Variations
in clinical chemistry values, if present, were not consistent with genotype
and, thus, were not considered phenotypically relevant.
Gene 268
Hematology
There were no significant differences detected in the homozygous mutant and
heterozygous mutant animals 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. The data were compiled from N0F2 and N1F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (74906, 76000, 83340)
3 homozygous mutant males (74894, 75995, 78632)
1 heterozygous mutant female (77655)
1 heterozygous mutant male (78633)
2 wild-type control females (74907, 83338)
2 wild-type control males (74896, 74902)
90 Day Cohort Mouse ID numbers are as follows:
1 homozygous mutant female (46962)
180 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (13263, 14935)
2 homozygous mutant males (14151, 15612)
4 wild-type control females (13264, 14159, 14934, 15081)
2 wild-type control males (14152, 15082)
300-360 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (11656, 13263, 50954, 51408)
4 homozygous mutant males (10827, 11655, 15612, 58101)
4 wild-type control females (13264, 51409, 51410, 51411)
3 wild-type control males (11212, 14152, 15084)
Although minor variations of hematological values were present in some animals,
these changes were not consistent with genotype and, thus, were not considered
phenotypically relevant.
Gene 268
Physical
Examination
Changes related to genotype:
The
following mice were evaluated by physical examination.
49 Day Cohort Mouse ID numbers are as follows:
5 homozygous mutant females (10796, 10799, 16040, 16042, 17646)
4 homozygous mutant males (10829, 18210, 19478, 19479)
1 heterozygous mutant female (16041)
1 heterozygous mutant male (18208)
2 wild-type control females (17458, 17459)
2 wild-type control males (18211, 19425)
300 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (10699, 10702, 11656, 13263)
5 homozygous mutant males (10827, 11655, 11657, 11658, 15612)
3 wild-type control females (10701, 13264, 51411)
3 wild-type control males (11212, 14152, 15084)
Mice were examined for the following observables: 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
appropriate gender.)
At 49 days, when compared to age- and gender-matched wild-type control mice, 5
of the 9 homozygous mice examined, 2 females (10796, 10799) and 3 males
(10829, 19478, 19479), had kinky tails.
There were no other genotype-related or biologically significant differences
noted between mutant and wild-type control mice at 49 days for any of the
parameters evaluated at physcial examination.
At 300 days (actual ages 303 to 450 days), when compared to age- and
gender-matched wild-type control mice, 1 male (10827) of the 9 homozygous
mutant mice had a kinky tail.
Occasional other differences in physical features of individual mutant mice were
present when compared to wild-type control mice. A mass in one homozygous
mutant male (10827) was a bulbourethral gland cyst histologically. Three
homozygous mutant mice (10827, 11655, 11656) had exophthalmos, which was
associated with Harderian gland inflammation in one female (11656), but was not
associated with histologic lesions in the other 2 mice. One homozygous
mutant male (15612) was squinting, and this was associated with a Harderian
gland adenoma. 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, procedural
artifacts, and/or findings of a nonspecific etiology. However, none of these
differences was regarded as genotype related.
Gene 268
Aging Metrics
Changes
related to genotype:
Body
weights and body lengths were measured for mice at 20, 49, 90, 180 and
300 days of age.
49 Day Cohort Mouse ID numbers are as follows:
8 homozygous mutant females (10699, 10702, 11656, 14157, 14935, 15078, 46962,
47116)
9 homozygous mutant males (11655, 11657, 11658, 14151, 14153, 14155, 15612,
46975, 47109)
8 heterozygous mutant females (10700, 11209, 11210, 11211, 14156, 15077, 15079,
15080)
7 heterozygous mutant males (11213, 11214, 11215, 11216, 14154, 15083, 15085)
4 wild-type control females (10701, 14159, 14934, 15081)
4 wild-type control males (11212, 14152, 15082, 15084)
90 Day Cohort Mouse ID numbers are as follows:
6 homozygous mutant females (10699, 10702, 11656, 13263, 46962, 47116)
5 homozygous mutant males (11655, 11657, 11658, 46975, 47109)
5 heterozygous mutant females (10700, 11209, 11210, 11211, 12873)
4 heterozygous mutant males (11213, 11214, 11215, 11216)
2 wild-type control females (10701, 13264)
1 wild-type control male (11212)
180 Day Cohort Mouse ID numbers are as follows:
6 homozygous mutant females (13263, 14157, 14935, 15078, 46962, 47116)
5 homozygous mutant males (14151, 14153, 15612, 46975, 47109)
4 wild-type control females (13264, 14159, 14934, 15081)
3 wild-type control males (14152, 15082, 15084)
300 Day Cohort Mouse ID numbers are as follows:
7 homozygous mutant females (10699, 10702, 11656, 13263, 14157, 14935, 15078)
7 homozygous mutant males (10827, 11655, 11657, 11658, 14151, 14153, 15612)
6 wild-type control females (10701, 13264, 14159, 14934, 15081, 51411)
4 wild-type control males (11212, 14152, 15082, 15084)
Body Weight and Length Findings:
When compared to age- (49, 90, 180, and 300 days) and gender-matched wild-type
control mice, the homzygous mutant mice had lower values for all 3 parameters
(body weight, body length, and body weight/body length ratio) at all time
points. Generally the differences between homozygous mutant and matched
wild-type control mice were greater for the males than for the
females. The body weight and the body weight/body length ratio decreased
for homozygous mutant males after 180 days of age. For each of the 3
parameters, the magnitude of the difference between wild-type control and
homozygous mutant males was greatest at 300 days of age.